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IMMUNOLOGY Directorate of Laboratory Medicine

Laboratory Medicine Copy No: Immunology Department Edition No: 004 Date of issue: 02/02/2011 Document No: IMM INS 001 Author: Immunology Management Team Authorised by: C Dennett 1 of 119

USER GUIDE

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Index About Us 3

Location and working hours 3 Quality Statement 3 Services Available 4 Accreditation 5 Quality Assurance 6 Scope of Service 7 How to Find Us 8 Staff Contact Details 9

Clinical conditions covered by the Immunology Department 11

Allergy / Hypersensitivity 13 Organ Specific Autoimmunity 17 Obstetrics and Gynaecology 20 Infection and Immunity 21 Malignancy 24 Neurology 26 Renal Disease 28 Rheumatology/Connective Tissue Disease Tests 31 Vasculitis 34

A-Z of clinical conditions and Immunological Tests 36 A-Z of Tests 39 Information for Patients 119

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About Us The laboratory offers a comprehensive test repertoire for the immunological investigation of patients. The four main areas covered include: Allergy, Autoimmunity, Cellular Immunology and Immunochemistry. We aim to provide a user-responsive service with rapid turn around of accurate results along with interpretive comments. Requests that are not covered by our service will be referred to other accredited specialist immunology laboratories.

Location and working hours The laboratory is situated in the Manchester Royal Infirmary, within the Clinical Science Buildings, and is open from Monday – Friday 08:30 to 17:00. It is closed on Bank Holidays. There is no out-of-hours service.

Quality Statement The Immunological investigations performed within the CPA accredited laboratory are recognised standards of practice. Documentation relating to internal quality control and quality assurance are retained for scrutiny by users of the Immunology Service.

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Services Available The Immunology Department aims to provide interpretative comments that are added to report forms. Referral for full clinical assessment is welcomed and is preferred for patients with suspected immune deficiency and those who are thought to have suffered an anaphylactic reaction. The laboratory is accredited with CPA and we participate in appropriate national quality assurance schemes. If you have any comments on the services that we provide please contact us by phone, letter or e-mail. Areas of clinical interest include: Allergy, Autoimmune Disorders and suspected Immune Deficiency. The Clinical Immunology staff provide a variety of specialist outpatient clinics as follows: Day/Frequency Speciality Clinical Support Provided Monday am Weekly Monday am Weekly

Primary Immunodeficiency Nurse Allergy Clinic

Dr Matthew Helbert Consultant Clinical Immunologist Sister Janet Hanrahan, Immunology Specialist Nurse

Tuesday am Fortnightly

Anaesthetic Clinic Dr Matthew Helbert, Consultant Clinical Immunologist Dr Nigel Harper, Consultant Anaesthetist

Tuesday am Weekly

Paediatric Clinic Dr Peter Arkwright, Consultant Paediatric Immunologist Dr Steven Hughes, Consultant Paediatric Immunologist

Wednesday pm Fortnightly Wednesday pm Weekly

Primary Immunodeficiency Follow-up Allergy Clinic

Dr Matthew Helbert Consultant Clinical Immunologist Sister Alex Farragher, Immunology Specialist Nurse

Thursday am Weekly Thursday pm Weekly

Allergy Clinic, including Desensitisation Allergy Clinic – including Latex Allergy

Dr Matthew Helbert, Consultant Clinical Immunologist Sister Alex Farragher, Immunology Specialist Nurse Sister Alex Farragher, Immunology Specialist Nurse

Friday am - approx every 4 weeks

Challenge day – Day Case admissions

Dr Matthew Helbert Consultant Clinical Immunologist Sister Alex Farragher, Immunology Specialist Nurse Sister Janet Hanrahan, Immunology Specialist Nurse

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Accreditation The Immunology Department is accredited by Clinical Pathology Accreditation (CPA), Health Professions Council (HPC) and the Conference of Post Graduate Medical Deaneries (COPMeD).

CPA Accredited Medical Laboratory

Reference No: 0866

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Quality Assurance The laboratory participates in all relevant quality assurance schemes and aims to maintain standards in all aspects of its work; however, problems will occasionally occur. Any complaints should be directed to the Clinical or Laboratory Managers – please make any reservations you may have about the quality of any aspect of the service known to us as soon as possible: we take your complaints very seriously. In particular, let us know of any untoward delay in receipt of reports, any discrepancies between results and clinical picture, and any errors in patient or clinician name on the report where samples have been referred to other laboratories for testing, this will be indicated on the report form. Please also let us know about new services you would wish to see developed.

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Scope of Service The range of immunology tests offered, together with the specimens required, are described in the A-Z of tests. A brief summary of the clinical applications of each test is provided – this is intended only as a guide. Additional background support is provided by links to clinical areas. Specimen Acceptance Policy The Directorate of Laboratory Medicine has a Specimen Acceptance Policy. A copy of the Directorate Specimen Acceptance policy is included in the DLM handbook obtained from the Client Services Office, CSB1 Request form The request form should contain a unique identifier, in addition to the minimum acceptance criteria listed below, so that the results of investigations can be accurately filed in the laboratory computer patient record. The request form data must match the three pieces of information that are on the samples – surname, forename or initial, date of birth or record number. Where there are multiple samples, taken at different times, the request form should include when with the times recorded. The times should also match the times written on the tubes. Each request form should also contain: NHS or Hospital Number Address for the report Consultant or GP Name of requestor Test(s) required

Date and time of sample when the time is important and when there are multiple samples

Sex Contact number for requestor Relevant clinical information If the above items are omitted, then it may not be possible to issue a report or to interpret results. In addition, the laboratory may not conduct some analyses if this information is not given. Appropriate comments will be made on the report. Additional Examinations The time limit for requesting additional examinations is restricted to two weeks. This restriction excludes requests for the unmasking of ENA and DNA results following a

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positive ANA result. The unmasking of ANA’s is restricted to 28 days from the date of the original assay.

How to Find Us The Immunology Department is located in the Manchester Royal Infirmary and is part of the Central Manchester University Hospitals NHS Foundation Trust (CMFT). The laboratory is situated within the Clinical Sciences Building III, and is open from Monday – Friday 08:30 to 17:00. It is closed on Bank Holidays. For a full map of the hospital site please click on this link: or if you have a paper copy type the following into your browser. http://intranet.cmht.nwest.nhs.uk/directorates/HSA/pdf/Manchester%20Hosps%20Inside%20Aug.09.pdf The full postal address is: Department of Immunology Directorate of Laboratory Medicine Clinical Sciences Building Manchester Royal Infirmary Oxford Road Manchester M13 9WL

http://intranet.cmht.nwest.nhs.uk/directorates/HSA/pdf/Manchester%20Hosps%20Inside%20Aug.09.pdf



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Consultant and Management Staff Contact Details Title: Clinical Manager and Consultant Immunologist

Name: Dr Matthew Helbert

Tel: 0161 276 6468

e-mail: [email protected]

CLINICAL INTERPRETATION

Title: Laboratory Manager

Name: Mr. Colin Dennett

Tel: 0161 276 6442/6468


MANAGERIAL INTERPRETATION

Senior Staff

Title: Chief Biomedical Scientist

Name: Philippa Coles

Tel: 0161 276 6440


TECHNICAL


Name: John Hewitt

Tel: 0161 276 6440


TECHNICAL


Name: Andrew Moran

Tel: 0161 276 6440


TECHNICAL

mailto:[email protected]





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Immunology Office

Title: Administration Manager

Name: Angela Bedford

Tel: 0161 276 6468


ADMINISTRATION

Immunology Clinical Support

Title: Immunology Specialist Nurse

Name: Alex Farragher

Tel: 0161 276 6186


NURSING ADVICE

Central Sample Reception

Title: Central Specimen Reception Manager

Name: Mary Hynes

Tel: 0161 276 4692


OPERATIONAL GUIDANCE

Title: Client Services Manager

Name: Colette McAlister

Tel: 0161 2766042


OPERATIONAL GUIDANCE

Results Hotline Tel: 0161 2768766 Other Contacts: Clinic Secretaries: 0161 276 6686/5653 Departmental Fax: 0161 276 6439





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Below is a list of clinical conditions covered by the Immunology department. In addition to this an A-Z list Immunological tests available is detailed below. Medical Category Clinical Conditions Covered Please click on a Medical Category for further information Allergy/Hypersensitivity Anaphylaxis, Asthma, Atopic Eczema

Bronchopulmonary eosinophilia Conjunctivitis Food Allergy and Intolerance Rhinitis Urticaria

Other Hypersensitivity Bronchopulmonary aspergillosis, Aspergilloma Hypersensitivity pneumonitis Bird fancier’s disease Farmer’s lung Coeliac disease

Organ Specific Autoimmunity Adrenal failure Chronic active hepatitis Dermatitis herpetiformis, Dressler’s Syndrome Gonadal failure Liver autoimmunity Pemphigus/Pemphigoid, Polyendocrine autoimmunity Primary biliary cirrhosis, Primary sclerosing cholangitis Thyroid disease

Obstetrics and Gynaecology Recurrent fetal loss Gonadal failure

Infection and Immunity Screening for exposure to tuberculosis HIV Screening for primary immunodeficiency Secondary cases of immunodeficiency Acquired C1-inhibitor deficiency Hereditary angioedema

Malignancy Lymphoproliferative disorders: Acute and Chronic Leukaemias, Lymphoma

Neurology Motor neuropathy, Myasthenia, Paraneoplastic syndromes

Renal Disease Goodpasture’s Syndrome IgA nephropathies

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Membranoproliferative glomerulonephritis Necrotising crescentic glomerulonephritis, Nephrotic syndrome

Rheumatology Polymyositis/Dermatomyositis Primary anti-phospholipid antibody syndrome Scleroderma/Systemic Sclerosis Screening Sjögren’s syndrome, Systemic lupus Erythematosus

Vasculitis Churg-Strauss Henoch-Schönlein Purpura Kawasaki’s syndrome Microscopic polyarteritis Primary systemic vasculitides Small vessel (hypersensitivity) vasculitis Wegener’s

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Allergy / Hypersensitivity

Brief Overview Requests for “RAST” are not acceptable. Requests should be for specific allergens as indicated by the history.

Allergy tests may help identify which allergens suggested by the history could cause symptoms. However, the finding of allergy specific IgE in the serum does not mean that the allergen is responsible for the symptoms under investigation, nor does it necessarily indicate that avoidance measures will help the patient. Specific IgE provides similar, although not identical, information to skin testing but is particularly valuable in assessing some groups of patients (young children, eczema/dermographism, taking antihistamines, past history of anaphylaxis), is needed to interpret the significance of the specific IgE. For each clinical condition, the relevant immunological tests are listed in blue together with a short explanation of their use. More detail, including the sample type required is available following the A-Z of tests. Patient information is available at: National Asthma Campaign: www.asthma.org.uk British Lung Foundation: www.lunguk.org National Eczema Society: www.eczema.org Anaphylaxis Campaign: www.anaphylaxis.org.uk Conjunctivitis

Allergen Specific IgE (limited association)

When the allergic reaction is strictly limited to the conjunctiva allergy tests are frequently negative. When conjunctivitis is part of a more generalised allergy, specific IgE and skin prick tests are usually positive for the causative allergen. Rhinitis

IgE and Allergen Specific IgE

Allergy tests may help distinguish allergic from vasomotor or other causes of rhinitis. Total IgE is often in the normal range or slightly elevated. Specific IgE may be sought to inhalant allergens. While the range of allergens tested should be sensibly guided by a careful history this should generally include allergens to which most

http://www.asthma.org.uk/

http://www.lunguk.org/

http://www.eczema.org/

http://www.anaphylaxis.org.uk/

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people are exposed, such as cat and house dust mite (HDM). Investigation of seasonal rhinitis is only indicated if there is some doubt about the diagnosis or if desensitisation is being considered. The pollens involved in seasonal rhinitis or asthma are as follows: grasses (May-Sept), trees (March-May) and weeds (July-September). There is little point in finding the exact pollen allergen unless it is intended to give the patient immunotherapy – when skin testing is mandatory.

Asthma

IgE and Allergen Specific IgE Total IgE is usually raised in extrinsic asthma; specific IgE to relevant allergens is also detectable. Specific IgE should invariably be sought against the house dust mite. Often this will suggest the appropriate animals (cats, dogs, horses etc). IgE to Aspergillus is associated with the need for closer monitoring and maybe more intensive steroid treatment. For seasonal asthma see seasonal rhinitis. Atopic Eczema

IgE and Allergen Specific IgE Total IgE is often markedly elevated in widespread disease and Specific IgE may be present at high level to allergens that cause no overt symptoms. Any positive Specific IgE results therefore need careful interpretation. Specific IgE to house dust mite is often high and house dust mite allergy may exacerbate eczema in such patients. Anaphylaxis

Mast cell tryptase and IgE and Allergen Specific IgE

Please refer all patients experiencing anaphylaxis to the allergy clinic for assessment. Blood samples for mast cell tryptase taken within 1-2 hours of reaction can help indicate if the reaction was anaphylactic. Anaphylaxis and anaphylactoid reactions to anaesthetics etc. Patients will be invited to attend the special clinic run jointly by Immunology and the Department of Anaesthesia at which they will be assessed. Acute Urticaria


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Total IgE and specific IgE may help identify the causal antigen involved in type I hypersensitivity. Bronchopulmonary eosinophilia

Allergen Specific IgE (to Aspergillus) Aspergillus fumigatus precipitins IgE ANCA (See vasculitic section)

Total IgE, specific IgE to Aspergillus, and Aspergillus precipitins (IgG) should identify cases due to hypersensitivity to the fungus. Total IgE may be raised in association with parasitic infestation. A positive ANCA may point to a vasculitic cause (Churg-Strauss). Food Intolerance


Evidence of specific IgE antibodies may be consistent with a diagnosis of food allergy but, unfortunately, the presence of such antibodies does not prove clinical sensitivity. Elimination and food challenge testing may help confirm or rule out food intolerances. Laboratory immunology tests cannot help investigate non-allergic food intolerance. Measurement of total IgE will permit the ratio of specific to total IgE to be assessed in positive samples.

Other Hypersensitivity Bronchopulmonary aspergillosis, Aspergilloma and Hypersensitivity pneumonitis

Aspergillus precipitins

In bronchopulmonary aspergillosis and aspergilloma a mixture of IgE and IgG antibodies are usually present. Bronchopulmonary aspergillosis can be caused by species other than A. fumigatus. In allergic rhinitis and asthma, where aspergillus is the relevant allergen, IgE antibodies dominate. In hypersensitivity pneumonitis, IgG antibodies are usually present alone. IgG antibodies, without IgE antibodies can also be seen in some cases of sub acute invasive aspergillosis. IgG antibodies are infrequent in healthy individuals. Aspergillus antibodies are not a recommended test for the investigation of the majority of cases of invasive aspergillosis in immunocompromised hosts.

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Farmer’s Lung

Farmer’s lung precipitins (thermophilic actinomyces)

Hypersensitivity to Micropolysporium faeni is a common cause of farmer’s lung hypersensitivity pneumonitis occurring 12 to 24 hours after exposure to mouldy hay. In some cases of farmer’s lung, hypersensitivity to other fungal species implicated. The absence of precipitin (IgG) to Micropolysporium faeni does not rule the diagnosis out. These antibodies can be found in some healthy individuals: The presence of these antibodies supports, but does not confirm, a diagnosis of farmer’s lung. There are numerous other causes of hypersensitivity pneumonitis including fungal spores and occupational antigens. Please discuss with the laboratory if these may be incriminated. The diagnosis is made by a combination of clinical features, X-ray and lung function tests. Bird fanciers Disease

Avian Precipitins

The symptoms are similar to farmer’s lung but more commonly are of the chronic type. Precipitins (IgG) to avian proteins provide good evidence of the cause of the symptoms. Coeliac Disease (Gluten sensitive enteropathy GSE) Patient information is available at: Coeliac Society: www.coeliac.co.uk

Ab to tissue transglutaminase Immunoglobulin levels IgG, IgA, IgM (IgA

may be required) IgA antibodies to tissue transglutaminase are found in active coeliac disease, and can be used to monitor compliance with treatment. Similar antibodies are seen in dermatitis herpetiformis. We may have to measure IgA to ensure that IgA deficiency (particularly common in these patients) is not causing a false negative result. IgG antibodies to tissue transglutaminase are utilized in IgA deficient patients.

http://www.coeliac.co.uk/

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Organ Specific Autoimmunity Brief Overview Requests for “autoimmune screen” are not acceptable. Requests should be for specific autoantibodies as indicated by the history. For each clinical condition, the relevant immunological tests are listed together with a short explanation of their use. More detail, including the sample type required are available below and at the end of the guide. Tests indicated in black are not routinely available or are offered by other laboratories. Patient information is also available at the following web address: http://www.niams.nih.gov/hi/topics/autoimmune/autoimmunity Thyroid goitre/nodule, hypo/hyperthyroidism

Ab to thyroid peroxidase (TPO) The levels of antibodies to thyroid peroxidase are closely related to the degree of lymphocytic infiltration in the thyroid. They are raised in autoimmune thyroiditis (90% of hypo-, >60% of hyper-) and both in post-viral and post-partum thyroiditis. They are less frequently raised in thyroid neoplasia/nodules/cysts, but their presence does not exclude these conditions.

Adrenal failure and Gonadal failure

Ab to adrenal cortex Ab to ovary Ab to testis

In this country, Addison’s disease is most often due to autoimmunity; the presence of antibodies to adrenal cortex suggests an autoimmune cause. There may also be antibodies to steroid producing cells of ovary and testis. A small proportion of cases of premature menopause are due to autoimmune oophoritis. Some of these patients also have adrenal failure – the same tests are done for both. Polyendocrine autoimmunity

Ab to adrenal cortex Ab to Ovary Ab to Testis Ab to thyroid peroxidase (TPO) Ab to islet cells Ab to gastric parietal cells

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In addition:

Antinuclear antibodies (includes anti-Centromere antibodies)

Ab to smooth muscle/mitochondrial Ab to acetylcholine receptors (if indicated)

Type 1: Usually presents under 10 yrs old, m=f. Hypoparathyroidism, adrenal failure and candidiasis also hepatitis, alopecia, delayed puberty, etc. Type 2: Occurs in adolescence/early adulthood, f>m, Addison’s + thyroid failure + type 1 diabetes mellitus M – maybe gonadal failure, vitiligo Type 3: Generally older, f>>m, autoimmune thyroiditis together with diabetes mellitus, gastric autoimmunity (GPC, anti-IF) – maybe other such as myasthenia. The spectrum of results may help confirm the diagnosis. Liver autoimmunity

Antinuclear antibodies (includes anti-Centromere antibodies)

Ab to smooth muscle/mitochondrial IgG IgA IgM electrophoresis Ab to LKM (Liver kidney Microsomal) Alpha-1-antitrypsin deficiency

(Biochemistry) Primary biliary cirrhosis (PBC) and autoimmune chronic active hepatitis (CAH) are associated with characteristic autoantibodies that are helpful in classifying the hepatitis and separating autoimmune CAH from the other forms. Patterns may include antibodies to smooth muscle (actin), reported as SMA-T in CAH, liver/kidney microsomal antibodies in LKM-positive autoimmune hepatitis and antibodies to mitochondria PBC. Centromere antibodies are also found in some cases of primary biliary cirrhosis. Presence of autoantibodies does not exclude a viral cause for the hepatitis. Because of the overlap between various different forms of hepatitis, it is usually best to test for all the types of autoantibody – AMA, SMA, LKM and ANA. There is a polyclonal increase in immunoglobulins in autoimmune and viral hepatitis, whilst a raised IgM is seen in primary biliary cirrhosis. Serum electrophoresis may reveal lack of alpha-1-antitrypsin if this is associated with the cirrhosis.

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Primary sclerosing cholangitis has no definitive serological markers, but may be associated with ANCA (anti-neutrophil cytoplasmic antibodies) or ANA or SMA. Pemphigus/Pemphigoid

Ab to skin Immunohistology

Blistering skin conditions may involve autoimmunity – antibodies are found to the epidermal intercellular “cement” in pemphigus, and to the epidermal basement membrane in pemphigoid. The pemphigus –like pattern is also seen in some patients with leprosy, burns, penicillin rashes, SLE, MG with thymoma, dermatomycoses, erythema multiforme etc – that of pemphigoid in herpes gestationis and epidermolysis bullosa acquisita. Dermatitis herpetiformis (DH)

Ab to tissue transglutaminase (tTG) Immunohistology

Though the diagnosis of DH is based on the appearance of the rash and IgA in the dermo-epidermal junction in the dermal papillae in biopsies, the presence of IgA antibodies to tTG may point to the association of DH with gluten sensitivity (see Coeliac disease). Dressler’s syndrome, post cardiotomy syndrome

Ab to cardiac muscle

Post-myocardial injury syndromes, including Dressler’s syndrome, are associated with the presence of anti-myocardial antibodies, which reflect the degree of cardiac damage.

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Obstetrics and Gynaecology Brief Overview Recurrent foetal loss

Anti-phospholipid antibodies Antibodies to cardiolipin (IgG and IgM)

Mid-trimester foetal loss may be due to thrombosis of placental vessels in anti-phospholipid syndrome (primary or associated with SLE). For additional information refer to: Rheumatology and Connective Tissue Disease tests Gonadal Failure

Ab to Ovary Ab to Testis Ab to adrenal cortex

This may be due to autoimmune damage to the gonads in males or females associated with antibodies to ovary, testis and adrenal cortex. (This is found with adrenocortical failure in autoimmune polyendocrinopathy).

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Infection and Immunity Please phone Immunology Clinical Staff ext 66468 to discuss the investigation of recurrent unusual infections Brief overview Primary immunodeficiency (PID) can cause preventable death or morbidity. Consider PID in patients with: - recurrent infection - severe infection - infection refractory to antibiotics - unusual infection Don’t forget that PID can present in childhood and adulthood as well as in infancy. Guidelines for testing are available at: www.ukpin.org.uk Patient information is available at: Primary Immunodeficiency Association: www.pia.org.uk Relevant immunological tests are listed below. More detail, including the sample required, is available at the end of this guide. Primary Immunodeficiency The following panels of tests are available for investigating patients: Immunoglobulin levels: IgG, IgA, IgM electrophoresis, IgG

subclasses Antibody responses: Functional antibodies

Hib/Pneumococcus Complement activity CH50 activity, Classical Pathway

C3, C4 Skin tests By arrangement T and B Cell subsets Tel: 0161 276 6440 Neutrophil function Tel: 0161 276 6440

http://www.ukpin.org.uk/

http://www.pia.org.uk/

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Background Grouping is frequently based on the specific fault in the immune system. This may include: - B Cell antibody deficiency causes mainly recurrent bacterial

infections - T cell deficiency causes viral, protozoal and fungal infections - Combined T and B cell deficiencies - Defective phagocytes - Complement deficiencies cause mainly bacterial infection. There are no “screening tests” for immune deficiency. In cases with recurrent bacterial infection it may be sensible to start by measuring immunoglobulins, but we advise discussing individual cases early on. Hereditary Angioedema

C1 esterase inhibitor C1 esterase inhibitor (functional test) C4

Recurrent abdominal pain and/or deep subcutaneous swellings without urticaria (particular occurring after minor trauma), often with family history, may indicate HAE. C4 and C1 inhibitor will be low. Uncommonly there may be normal C1INH level with defective function. If C4 is very low without other explanation and C1INH normal, C1INH function will be measured. Secondary Immunodeficiency

Immunoglobulins IgG, IgA, IgM, electrophoresis

Monitoring absolute CD4 counts (for patients with known HIVserology)

Secondary causes of immunodeficiency are more common than primary causes and levels of immunoglobulins might reflect decreased production (eg. lymphoproliferative disorders, drugs) or increased losses (nephritic syndrome). In HIV infection the CD4 count is used to monitor progress of disease and inform treatment decisions. Other acute and chronic diseases affect CD4 counts. In HIV infection they are best done at the same time of day each time and avoiding acute ill health. They should never be done as a substitute to HIV antibody testing to diagnose HIV infection.

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Guidelines and information on CD4 counts are available at: www.aidsmap.com

Additional patient information is available at: National Aids Trust: www.nat.org.uk Terrence Higgins Trusts: www.tht.org.uk Acquired C1 esterase inhibitor deficiency

C1 esterase inhibitor C1q C3 C4

Consumption/inactivation of C1INH may occur in SLE and

lymphoproliferative disease. This may lead to episodes of angioedema as with the inherited form. C1q is low in acquired C1INH deficiency but usually normal in HAE.

Patient information is available at: Primary Immunodeficiency Association: www.pia.org.uk TB Exposure: Quantiferon This test measures gamma interferon produced by T cells in response to M. tuberculosis peptides. The test is used to help diagnose latent TB infection and is indicated in individuals with a positive delayed hypersensitivity skin test. The test may produce indeterminate results in patients with active TB and in immune deficiency states.

Quantiferon

http://www.aidsmap.com/

http://www.nat.org.uk/

http://www.tht.org.uk/


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Malignancy

Brief Overview Flow cytometry is a useful aid to the diagnosis of leukaemias and lymphomas. Cells from blood, marrow or fresh lymph node can be studied. Flow cytometry works when: - The sample is fresh (<12 hours old) - There are clear clinical details - Marrow samples should be placed in special medium, available

from the laboratory - Lymph node biopsies should not be formalin fixed Flow cytometry may also be used to assess whether Leukaemia or lymphoma has gone into remission after chemotherapy. Finally, flow cytometry can be used to measure the number of circulating stem cells prior to stem cell transplantation. See: http://www.bcshguidelines.com for more information and guidelines. The demonstration of paraproteins by electrophoresis is one of the criteria required for a diagnosis of multiple myeloma. Their quantification, the degree of associated immunosuppression of other immunoglobulins and the excessive proliferation of plasma cells in the bone marrow are all laboratory indicators of a malignant paraproteinaemia. Serum levels of β2-microglobulin are useful indicators of prognosis, partly reflecting the degree of renal damage (and are raised in other causes of renal failure, malignancies, and some autoimmune disorders). Serum free light chain estimation is a useful adjunct to the diagnosis and monitoring of myeloma. For each clinical condition, the relevant immunological tests are listed together with a short explanation of their use. More detail, including the sample type required is available at the end of this guide. Tests indicated in black are not routinely available or are offered by other laboratories. Lymphoproliferative disorders

Immunophenotyping for lymphoid and myeloid malignancies

Chronic lymphocytic malignancies/lymphoma panel

Acute Leukaemia panel

http://www.bcshguidelines.com/

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Stem cells Patient information is available at:

Leukaemia Research Fund: www.lrf.org.uk Lymphoma association: www.lymphoma.org.uk Paraproteinaemia Serum protein electrophoresis/densitometry:

IgG, IgA, IgM electrophoresis, Serum Free Light Chains

Urinary Light Chains

Bence-Jones protein Immunofixation

Uses electrophoresis sample β2-microglobulin

β2 microglobulin Patient information is available at: International Myeloma Federation (UK): www.myeloma.org.uk

http://www.lrf.org.uk/

http://www.lymphoma.org.uk/

http://www.myeloma.org.uk/

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Neurology

Brief Overview Myasthenia

Ab to acetylcholine receptors Ab to thyroid peroxidase (TPO)

Impaired neurotransmission in MG is caused by the presence of antibodies to acetylcholine receptor. Associated autoantibodies to skeletal muscle and thyroid microsomes are sometimes also detected. Although antibodies to acetylcholine receptor (AChR) are present in all patients with Myasthenia Gravis, they are detectable in only 90% of sera tested in the laboratory. They are particularly difficult to detect in patients with ocular myasthenia, where up to 40% of patients have undetected antibodies. Antibodies to striated muscle are present in 30% of patients with MG – and 60% of these will also have a thymoma. This test is insufficiently reliable to help in management and is no longer performed. Motor Neuropathies - IgM antibodies to ganglioside GM1 Anti-ganglioside GM1 antibodies are present in 80% of patients with pure motor weakness with evidence of multifocal conduction block. Low titre anti-ganglioside antibodies are present in some sensori-motor neuropathies, SLE, other autoimmune disease and normal controls. Antibodies associated with other neurological conditions - Antibodies to Myelin associated glycoproteins (MAG)

MAG antibodies are detected in 50-75% or patients with IgM paraproteinaemia and peripheral neuropathy. - Paraneoplastic antibodies (Yo, Hu and Ri) Anti-Yo antibodies have been found in paraneoplastic cerebellar degeneration Anti-Hu antibodies have been found in paraneoplastic encephalomyelitis and in sensory neuropathy. Anti-Ri antibodies can be observed in patients with rapidly progressive brainstem tumour.

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A negative test result does not exclude the possibility of a paraneoplastic syndrome.

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Renal Disease Brief Overview Acute renal presentations: Immunological processes are implicated in many renal diseases. In several situations, diagnosing and treating immunological processes can halt or reverse renal impairment. For this reason the following tests may be offered on an urgent basis, provided an urgent request is made by phone. Immunological test Clinical condition Turnaround

time ANCA Vasculitis Same day Anti glomerular basement membrane

Goodpasture’s disease

Same day

ANA SLE and other connective tissue diseases

Same day

Serum and urine electrophoresis

Myeloma Results next day

C3, C4 Immune complex nephritis

Results next day

Chronic renal presentations The same tests listed above are also useful for the diagnosis of chronic renal disease. Cryoglobulinaemia may also be excluded in some patients with chronic renal failure. This test requires very careful specimen handling and it may be helpful to screen for cryoglobulinaemia by doing C4; if C4 is normal, cryoglobulinaemia is very unlikely. C3 nephritic factor can cause membranoproliferative disease. The laboratory can refer samples to a laboratory that measures C3 nef directly, but this is a complex test with delayed results. We recommend checking C3 first; if C3 is normal, C3 nef is very unlikely to be present. Some of these tests are also used to monitor renal disease (ANCA, C4). In SLE, monitoring anti-DNA antibody levels and complement C4 is more useful than monitoring ANA. The half life of IgG antibodies is about three weeks, so most forms of immunosuppressive treatment will not produce rapid changes in

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autoantibodies and repeat sampling more than every six weeks is probably unhelpful. The exceptions are plasmapheresis and administration of high dose IVIg, which cause rapid and clinically meaningful fluctuations in autoantibody level. In these situations, more frequent testing of ANCA or anti-GBM is appropriate. Relevant immunology tests for specific clinical conditions are listed below: Patient information is available at: National Kidney Federation: www.kidney.org.uk Screening for Glomerulonephritis First occasion:

C3 C4 Antinuclear antibodies (includes Anti-

Centromere antibodies ) Neutrophil cytoplasmic antibody (ANCA) Cryoglobulins

Additional tests may help categorise the type of glomerulonephritis Membranoproliferative glomerulonephritis

C3 C3 nephritic factor (only if C3 very low)

Serum C3 levels are low in some forms of membranoproliferative glomerulonephritis reflecting the presence of the circulating autoantibody C3 nephritic factor which binds and activates C3 convertase. Glomerulonephritis

Ab to glomerular basement membrane (GBM)

Ab to proteinase3, PR3 (c-ANCA) Ab to myeloperoxidase, MPO (p-ANCA)

p-ANCA associated glomerulonephritis is the common form of Necrotising crescentic glomerulonephritis, reflecting different vasculitic causes.

http://www.kidney.org.uk/

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Goodpasture’s syndrome Ab to glomerular basement membrane

(GBM) A combination of renal and lung involvement may suggest Goodpasture’s syndrome due to the presence of antibodies to the glomerular basement membrane (GBM). IgA Nephropathy

Serum Immunoglobulins IgG, IgA, IgM, electrophoresis

Serum IgA may be raised in IgA nephropathies including Henoch Schönlein purpura. Nephrotic syndrome

Serum Immunoglobulins IgG, IgA, IgM, electrophoresis

Serum immunoglobulins may be low in poorly selective proteinuric forms of nephrotic syndrome (focal glomerulonephritis). ATG monitoring: Patients receiving ATG therapy have T cell numbers (% and absolute counts) monitored daily. For the result to be available by noon, it is essential that the sample is received in the laboratory no later than 10:30am.

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Rheumatology/Connective Tissue Disease Tests Background The tests described in this section are very non-specific. Some (ANA, rheumatoid factor) are found in completely healthy people, particularly older women. These can also be transiently positive in infection or as the result of drugs (particularly anti DNA). This means that these tests should not be used as a “screen” for investigating patients with raised ESR’s or general malaise. Rheumatoid factor is especially prone to misinterpretation. It is resent in 15% of normal individuals and is not diagnostic of rheumatoid arthritis. Rheumatoid arthritis is diagnosed by finding symmetrical peripheral polyarthritis with erosions on X-ray. The half-life of IgG antibodies is about three weeks, so most forms of treatment will not produce rapid changes in autoantibody levels and repeat sampling more than every six weeks is probably unhelpful. We would advocate that it is nearly never useful to repeat positive ENA antibodies. Each specific test is highlighted in blue. More information including sample requirements and turnaround times can be found at the end of this guide Patient information is available at the following sites: British Society for Rheumatology: www.rheumatology.org.uk Lupus UK: www.lupusuk.com Raynaud’s and Scleroderma Association: www.raynauds.org.uk Arthritis Research Campaign: www.arc.org.uk Screening for Systemic Autoimmune Disease

Antinuclear antibodies (includes anti Centromere antibodies)

Rheumatoid factor Raised immunoglobulins, IgG, IgA, IgM,

electrophoresis Systemic Lupus Erythematosus


http://www.rheumatology.org.uk/

http://www.lupusuk.com/

http://www.raynauds.org.uk/

http://www.arc.org.uk/

Department of



Ab to double stranded DNA (IgG); Ab to Crithidia (if appropriate)

Ab to ENA includes: Sm, Sm/RNP, RNP(RNP A, RNP68), Ro(SS-A52 SS-A60), La(SS-B), Ribo P, Scl-70, Jo-1 and Chromatin

Ab to cardiolipin (IgG and IgM) IgG, IgA, IgM, electrophoresis Complement components C3, C4 Classical pathway activity CH50 B cell enumeration

Criteria for the diagnosis of SLE include antinuclear antibodies (ANA), antibodies to ds DNA, (Crithidia assay if appropriate) antibodies to extractable nuclear antigens (ENA) and anti cardiolipin antibodies. The presence of particular groups of serum antibodies may be associated with different clinical patterns of disease activity. Other typical immunological findings include raised serum IgG, and low serum complement levels (C3, C4) as well as the presence of rheumatoid factor, and other autoantibodies. DNA antibody levels, C4 levels (and ESR) are of some help in monitoring disease activity. Sjögren’s syndrome



Rheumatoid factor There may be considerable overlap with other autoimmune disorders, including SLE. Characteristically antinuclear antibodies and antibodies to extractable nuclear antigens (particularly antibodies to Ro or SS-A, and antibodies to La or SS-B) are found. Rheumatoid factor and raised immunoglobulins may be found. Scleroderma/Systemic sclerosis



Department of



The Scl-70 antibody is associated with systemic sclerosis, whilst centromere antibodies are found in limited systemic sclerosis (CREST syndrome). Polymyositis/Dermatomyositis



Jo-1 antibodies are found in a subset of myositis patients, especially those with interstitial lung disease. Antiphospholipid antibody syndrome

Antibodies to phospholipids Ab to cardiolipin (IgG and IgM)

Lupus anticoagulant (Haematology) Recurrent arterial or venous thrombosis (or foetal loss) may be associated with antibodies to phospholipids including cardiolipin. Related antiphospholipid antibodies include the lupus anticoagulant. Cardiolipin antibodies may be found in other autoimmune disorders, particularly SLE and are also seen very frequently in acute and chronic infections. Guidelines suggest that 2 positive tests (anticardiolipin antibodies, “lupus anticoagulant” –haematology) more than 6 weeks apart are required to diagnose antiphospholipid syndrome. More information is available at: www.bcshguidelines.com

http://www.bcshguidelines.com/

Department of



Vasculitis Brief Overview The term vasculitis refers to inflammation of blood vessels and represents a heterogeneous group of clinical disorders. Each form of vasculitis can produce a distinct clinical picture, but in many cases immunology testing can differentiate, confirm and monitor the presence of vasculitis. Other forms of vasculitis, for example, Behçet’s disease and primary cerebral vasculitis are not associated with any specific blood tests. The main immunological tests are antinuclear antibody (ANA –for SLE a connective tissue diseases) and anti-neutrophils cytoplasmic antibody (ANCA - Wegener’s granulomatosis and other vasculitides). It is important to understand that neither of these tests are specific; they can both be positive in infection and in liver disease. This makes these tests very unsuitable as “screens” in patients with vague symptoms such as malaise, weight loss or fever. Other tests include complement C3 and C4, which are altered in immune complex disease and cryoglobulin. Small vessel hypersensitivity vasculitis

Antinuclear antibodies Rheumatoid factor Complement C3, C4 Cryoglobulins Serum immunoglobulins Anti-neutrophil cytoplasmic antibodies

(ANCA) CRP (Biochemistry)

Infection, drugs, foreign proteins (as examples) may be causal factors in a vasculitis affecting predominantly the skin. Immunological findings may sometimes include raised ESR/CRP, depressed levels of complement factors suggesting consumption, and the presence of antinuclear antibodies and rheumatoid factor (low titre). General screening tests for vasculitis should also include serum immunoglobulins, and ANCA (see below). If there is evidence for more extensive visceral involvement, one of the primary systemic vasculitides may be involved (see below). Alternatively, the vasculitis may be secondary to autoimmune disease (eg. SLE, chronic active hepatitis – see earlier section),

Department of



neoplasia (eg. lymphoma), cryoglobulinaemia (these are immunoglobulins that form precipitates in the cold). Primary systemic vasculitis

Anti-Neutrophil cytoplasmic antibodies (ANCA)

Anti-Myeloperoxidase (MPO) Anti-Proteinase 3 (PR3) Immunoglobulins (IgG, IgA, IgE) CRP (Biochemistry)

Some forms of systemic vasculitis are strongly associated with circulating anti-neutrophil cytoplasmic antigens (ANCA). In Wegener’s Granulomatosis, (WG) (lung, renal) there is a diffuse cytoplasmic pattern (c-ANCA), as well as polyclonal elevations of IgG, IgA, IgE and raised CRP. ANCAs with a perinuclear pattern (p-ANCA) are seen in some patients with polyarteritis nodosa, (PAN) (weight loss, musculoskeletal, renal) and Churg-Strauss (“asthma”, eosinophilia, hypocomplemenaemia, raised IgE). Both types of ANCA may be seen in microscopic polyarteritis (MPA) (clinical overlap between classic PAN and WG). Atypical forms of ANCA reactivity may be seen in association with Henoch-Schönlein Purpura (sometimes IgA raised), Kawasaki’s syndrome, and in other autoimmune disorders (eg. SLE, ulcerative colitis).

Department of



A-Z of clinical conditions and Immunological Tests…. Clinical Condition Immunological Test Link(s)

A Acute leukaemia Cell marker panel CD2, CD10, CD13,

CD14, CD19, CD33, CD34, CD79a, CD117, TdT and MPO

Adrenal failure Ab to adrenal cortex, Ab to Ovary, Ab to Testis

Anaphylactoid reactions to drugs etc Refer patients to the combined Immunology/Anaesthetic clinic

Anaphylaxis IgE, Mast cell tryptase Angioedema (Hereditary) C1 esterase inhibitor. C1 esterase

inhibitor functional Asthma IgE, Specific IgE Atopic Eczema IgE, Specific IgE

B-C B cell enumeration Immune deficiency panel Bird Fancier’s Disease Avian precipitins Bronchopulmonary Aspergillosis Aspergillus precipitins (Aspergillus

fumigatus) C1 esterase inhibitor deficiency (acquired) C1 esterase inhibitor, C1q, C3, C4 Chronic lymphocytic malignancies/lymphoma

Cell marker panel: CD3, CD5, CD19, CD23, CD79b,Kappa chains, Lambda chains, FMC7, CD38

Coeliac Disease Ab to tissue transglutaminase Conjunctivitis Specific IgE Cryoglobulinaemia (mixed) Cryoglobulins

D-G Dermatitis herpetiformis Ab to tissue transglutaminase Dressler’s syndrome Ab to cardiac muscle Farmer’s Lung Farmer’s lung precipitins

(Micropolysporium faeni) Gonadal Failure Ab to Ovary, Ab to Testis, Ab to

adrenal cortex Goodpasture’s syndrome Ab to glomerular basement

membrane

H-M IgA nephropathies Raised IgA, IgG, IgM electrophoresis Immunodeficiency (Primary) Immunodeficiency panel Immunodeficiency (Secondary), HIV Immunoglobulins IgG, IgA, IgM,

electrophoresis; CD4 for patients with known HIV serology

Lymphoproliferative disorders Immunophenotyping for lymphoid and myeloid malignancies (full clinical

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information required) Liver autoimmunity Ab to smooth muscle/mitochondrial;

Liver kidney microsomal (LKM), IgG, IgA, IgM, electrophoresis

Lymphoid/myeloid malignancies Cell surface markers appropriate to diagnostic information provided

Mixed connective tissue disease Antibodies to ENA, particularly RNP Ab to ENA including Sm, Sm/RNP, RNP(RNP A, RNP68), Ro(SS-A52 SS-A60), La(SS-B), Ribo P, Scl-70, Jo-1 and Chromatin

Motor neuropathy Anti-ganglioside antibodies (GM1) Myasthenia gravis Antibodies to acetylcholine receptor

(AchR)

N-P Necrotising crescentic glomerulonephritis Ab to myeloperoxidase MPO (p-

ANCA) Nephrotic syndrome IgG, IgA, IgM, electrophoresis Paraproteinaemia, Myeloma IgG, IgA, IgM, electrophoresis

(including immunofixation) Serum Free Light Chains Bence-Jones protein: β2 microglobulin

Pemphigus/Pemphigoid Ab to skin, Immunohistology Polyendocrine Autoimmunity Ab to adrenal cortex, Ab to Ovary, Ab

to Testis, Ab to islet cells, Ab to gastric parietal cells. Additional: Antinuclear antibody (includes anti-centromere Abs). Ab to smooth muscle/mitochondrial, Ab to acetylcholine receptors (if indicated)

Polymyositis/Dermatomyositis Antinuclear antibodies, antibodies to Jo-1 ENA includes: Sm, Sm/RNP, RNP(RNP A, RNP68), Ro(SS-A52 SS-A60), La(SS-B), Ribo P, Scl-70, Jo-1 and Chromatin

Primary anti-phospholipid antibody syndrome

Anti-phospholipid antibodies, Ab to cardiolipin (IgG, IgM)

R-S Recurrent foetal loss Ab to phospholipids, Ab to cardiolipin

(IgG, IgM) Rhinitis IgE, specific IgE Scleroderma/systemic sclerosis Antinuclear antibody includes anti-

centromere antibodies (CREST). Antibodies to Scl-70. ENA includes: Sm, Sm/RNP, RNP(RNP A, RNP68),

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Ro(SS-A52 SS-A60), La(SS-B), Ribo P, Scl-70, Jo-1 and Chromatin

Sjögren’s syndrome Antinuclear antibodies, antibodies to extractable nuclear antigens (ENA) includes Ro, La

SLE Antinuclear antibodies (includes anti-centromere) Ab to double stranded DNA (IgG) Ab to ENA includes: Sm, Sm/RNP, RNP(RNP A, RNP68), Ro(SS-A52 SS-A60), La(SS-B), Ribo P, Scl-70, Jo-1 and Chromatin Other indicators include: Raised IgG IgG, IgA, IgM, electrophoresis, Low complement C3,C4

Systemic Autoimmune Disease Antinuclear antibodies (includes anti-centromere) Rheumatoid Factor, IgG, IgA, IgM, electrophoresis

T-V TB (latent) Gamma Interferon (Quantiferon) Thyroid Disease Ab to thyroid peroxidase (TPO) Urticaria (Acute) IgE, Specific IgE Vasculitis (Primary systemic) – Wegener’s, Churg-Strauss, Microscopic polyarteritis, Henoch-Schönlein Purpura, Kawasaki’s syndrome

Antinuclear antibody (includes anti-centromere) Ab to myeloperoxidase MPO (p-ANCA) Ab to proteinase 3 PR3 (c-ANCA) Serum immunoglobulins IgG, IgA, IgM electrophoresis IgE (Total), CRP (Biochemistry)

Vasculitis (small vessel hypersensitivity) Antinuclear antibodies (includes anti-centromere) Rheumatoid factor, Complement C3, C4, Cryoglobulin Serum immunoglobulins IgG, IgA, IgM, electrophoresis Neutrophil cytoplasmic antibody (ANCA)

W-Z

Department of



A-Z of Tests Acute Leukaemia panel CD2, CD10, CD13, CD14, CD19, CD33, CD34, CD79a, CD117, TdT, MPO Acetyl Choline Receptor Antibodies Myasthenia Gravis Adrenal antibody The results are positive in 60-7-% of patients with idiopathic Addison’s disease. Anti-adrenal antibodies are also present in 28% of patients with idiopathic hypothyroidism and 7% of patients with Hashimoto’s disease. Allergy specific IgE (ImmunoCAP®) Measurement of allergens specific IgE is of value where skin testing is difficult for any reason. Over 100 specific allergens (request panel) are routinely available and can be viewed by selecting the link below. Any requests for allergens that are not on the list should be discussed with a clinician. Amphiphysin Anti-Basal Ganglia Antibodies Anti-C1q Anti-neutrophil cytoplasmic antibody (ANCA) Anti-neutrophil cytoplasmic antibodies (ANCA) are found in several types of vasculitis. Samples for ANCA are initially tested by immunofluorescence on neutrophils. Positive samples are then further tested by Multiplex assay for specific antibodies to either proteinase 3 (PR3) or myeloperoxidase (MPO). In general, a classical cANCA pattern corresponds to PR3 reactivity whilst a perinuclear pANCA pattern corresponds to MPO reactivity. Atypical ANCA patterns do not usually correlate with either antigen. These tests are used to diagnose vasculitis and to monitor disease activity. Infections and autoimmunity can produce positive tests reducing the specificity of ANCA testing. Antinuclear antibody (ANA), includes anti-centromere Indicated in the investigation of suspected “connective tissue disorders”. The absence of ANA almost excludes a diagnosis of SLE. Antinuclear antibodies are detected in other clinical conditions including: Sjögren’s syndrome, systemic sclerosis (CREST), chronic active hepatitis, fibrosing alveolitis, juvenile chronic arthritis and infections. Aquaporin 4

Department of



Aspergillus fumigatus precipitins These tests detect presence of IgG antibodies to Aspergillus fumigatus. Aspergillus precipitins. See also: - Farmer’s lung and Avian precipitins. Avian precipitins As for Aspergillus precipitins. B cell enumeration This can be used to monitor patients receiving Rituximab. We recommend a pre-treatment baseline sample. See immunodeficiency panel. Bence Jones protein (Urinary light chains) Urine immunofixation Β2 Microglobulin High levels are seen in connective tissue disease e.g. Sjögren’s, RA, Granulomatous disease like sarcoidosis, CVID. C1 esterase inhibitor Should always request C4 at the same time. C1 esterase inhibitor functional test C1q Reduced levels in acquired angiodema and urticarial vasculitis. C3 Nephritic Factor Mesangiocapilliary glomerulonephritis (only if C3 is low) Cardiac muscle antibodies Associated with Dressler’s syndrome. Cardiolipin (IgG and IgM) antibodies Found in the anti-phospholipid syndrome, which may be primary or occur as a secondary complication of SLE. Raised levels are significantly associated with the presence of both venous and arterial thrombosis, thrombocytopaenia and recurrent foetal loss. CD34 (Stem cells) CD3 (T cells) CD4 count (T cell count) (for patients with known HIV serology) The CD4 count is used to monitor disease progression in HIV infection. For example, patients with counts below 200 cells/ul are at risk of pneumocystis pneumonia and should receive antibiotic prophylaxis. CD4 counts are also used to assist decision

Department of



making on anti-retroviral therapy. BHIVA publish guidelines on CD4 counts and their interpretation. www.aidsmap.com Apart from HIV infection, the CD4 count can be reduced by acute and chronic stress, including infections and physical or psychological stress. CD4 counts are also affected by daily circadian rhythms and the menstrual cycle. CH100 complement activity Classical Pathway Chronic lymphocytic malignancies/lymphoma panel Panel of markers used: CD3, CD5, CD19, CD23, CD79b, Kappa chains, Lambda chains, FMC7, CD38 Complement C3 Complement C4 Useful in monitoring a wide range of inflammatory and autoimmune disorders. Single point determinations are of limited value and serial measurements are recommended. Crithidia antibodies Used for the detection of antibodies that are specific for double-stranded DNA. Cryoglobulins Careful attention to specimen collection is required. Cyclic citrullinated peptide (CCP) antibodies Double-stranded DNA antibodies (IgG) The presence of autoantibodies to double-stranded DNA is strongly suggestive of SLE although they are detected in 40-60% of patients with this disease. ENA antibodies includes: Ro (SS-A 52, SSA-60), La (SS-B), Sm, Sm/RNP, RNP (RNP A, RNP 68), Ribo P, Chromatin and Jo-1, and Scl-70 Antibodies to extractable nuclear antigens are of use in the classification of clinical subsets of connective tissue disorders and in providing prognostic information. Farmer’s lung precipitins These tests detect the presence of IgG antibodies to Micropolysporium Faeni (Farmer’s lung precipitins). Free Light Chains (serum) Myeloma diagnostics Ganglioside Antibodies GM1 Guillian-barre syndrome, demyelinating polyneuropathy, multifocal motor neuropathy Ganglioside Antibodies GQ1b


Department of



Miller-Fisher syndrome Gamma Interferon (Quantiferon) Glomerular basement membrane antibodies Diagnostic test for Goodpasture’s syndrome. Glutamic Acid Decarboxylase (GAD) IDDM, Stiff-man syndrome Histone Antibodies Drug-induced SLE, Positive in RA/SLE etc. IgD (Immunoglobulin D) Familial Mediterranean fever IgE (Total) IgG subclasses IgG1,2,3,4 Immunodeficiency (Contact on 0161 276 6440 to discuss) Immunoglobulins (IgG, IgA, IgM) IgA: raised in elderly, chronic infection, cirrhotic liver disease IgM: raised primary biliary cirrhosis, acute infection, EBV, CMV, TB. Marked polyclonal IgG elevation is seen in HIV, viral and autoimmune hepatitis, Sjögren’s and sarcoidosis. Less marked elevation in chronic inflammatory and infective conditions. Immunophenotyping for lymphoid and myeloid malignancies (full clinical details required) Cell surface markers appropriate to diagnostic information provided. Insulin Antibodies Insulin resistance Islet Cell Antibodies Predictive of future insulin requirement in patients presenting with NIDDM* and in relatives of IDDM* patients. Mannose Binding Lectins Recurrent infection in childhood Mast cell tryptase

Department of



Muscle Specific Tyrosine Kinase (MUSK) Myelin Associated Glycoprotein (MAG) IgM monoclonal neuropathy Myeloperoxidase (MPO) antibodies Autoantibodies to myeloperoxidase are found in the sera of patients with various types of systemic vasculitis, including (idiopathic crescentic glomerulonephritis), Churg-Strauss syndrome, microscopic polyangiitis and polyarthritis nodosa. Neonatal IgG Ovary antibodies Autoantibodies to the ovary may interfere with fertility by masking functional proteins on the cell surface of ovaries and interfering with intracellular protein functions. Paraneoplastic Antibodies (Hu, Yo, Ri) PR3 autoantibodies (cANCA) c-ANCA’s are directed to proteinase 3 and are typically associated with Wegener’s granulomatosis. Rheumatoid factor Serum free light chains Serum paraprotein identification/quantification Additional information is provided under Serum Protein Electrophoresis and Bence Jones protein (urine immunofixation). Serum Protein Electrophoresis (see IgG, IgA, IgM electrophoresis) Skin antibodies Two types of skin autoantibodies that detect different skin components are recognised: Intercellular cement substance (Pemphigus antibodies) Basement membrane antibodies (Pemphigoid antibodies) Smooth muscle/mitochondrial antibodies (Including liver kidney microsomal (LKM), gastric parietal cell (GPC) and ribosomal). Smooth muscle antibodies at a high titre are associated with chronic active hepatitis, and at low titres are more likely to be triggered by infection. Mitochondrial antibodies are associated with primary biliary cirrhosis.

Department of



Testis antibodies Thyroid peroxidase (TPO) antibodies TPO is the immuno-active microsomal antigen. Tissue transglutaminase Acts as a screening test for coeliac disease/dermatitis herpetiformis. TSH Receptor Antibodies Thyroid disorders/pregnancy/Graves disease. Risk of post-partum or neonatal thyroid dysfunction Voltage-gated Calcium Channel Antibodies Voltage-gated Potassium Channel Antibodies The relevant tests required will be specified for each individual case. Referred tests are printed in black.

Department of



Acetylcholine receptor antibody Referred to: Department of Immunology

PO Box 894 Sheffield S5 7YT

General Information Acts as a confirmatory test for myasthenia gravis

o Specimen transport: At room temperature o Repeat Frequency: At change of clinical symptoms

o Special precautions: None

Laboratory Information

Normal Reference

Range

Volume and sample type

Method

Turnaround time

(calendar days from sample receipt to authorised result)

Median 16 <0.2 nmol/L

7 ml clotted blood

Radio

immunoassay 95th

percentile 34

Clinical Information

o Indications for the test 90% of patients with generalised myasthenia gravis and about 60-70% of patients with ocular myasthenia have detectable AChR antibodies. Can be used to monitor disease activity, but antibodies may persist in 60% of patients even if disease is in remission. The assay also detects antibodies to the fetal form of the AChR in mother of fetuses with Arthrogryposis multiplex congenital.

o Factors affecting the test

Clinical workstation reference: ACH-R Ab to acetylcholine receptor

Department of



Acute Leukaemia panel General Information Panel of markers used: CD2, CD10, CD13, CD14, CD19, CD33, CD34 CD79a, CD117, Tdt, MPO

o Specimen transport: At room temperature o Repeat Frequency:

o Special conditions / precautions: Do not refrigerate samples


Reporting Units


Method

Turnaround time


Median 2 Percentage*

10 mls EDTA blood of 5 mls

bone marrow in heparin with

tissue culture medium

Flow Cytometry

95th percentile

7


o Indications for the test Suspected acute Leukaemia.


Clinical workstation reference: ACUTE Acute Leukaemia panel

Department of



Adrenal antibody General Information The results are positive in 60-70% of patients with idiopathic Addison’s

disease. Anti-adrenal antibodies are also present in 28% of patients with idiopathic hypothyroidism and 7% patients with Hashimoto’s Disease.

o Specimen transport: At room temperature o Repeat Frequency: At significant change of clinical symptoms



Normal

Reference Range


Method

Turnaround time

(calendar days from sample receipt to

authorised result)) Median 3

Neg

7 ml clotted

blood

Immunofluorescence 95th

percentile 8


o Indications for the test Addison’s Disease with associated other organ-specific autoimmune conditions. Patients with chronic mucocutaneous candidiasis with endocrinopathy.


None

Clinical workstation reference: ADRENAL Ab to adrenal cortex

Department of



Allergen Specific IgE (ImmunoCAP®) General Information Measurement of allergen specific IgE is of value where skin testing is difficult

for any reason. Over 100 specific allergens are routinely available. Any requests for allergens that are unusual should be discussed with a clinician.

o Specimen transport: At room temperature o Repeat Frequency: >1 year unless marked changes in allergic

condition

o Special precautions: None Laboratory Information

Normal Reference

Range


Method

Turnaround time


Median 1 <0.4 kUA/l

7 ml clotted blood

(14 ml required for multiple allergens)

ImmunoCAP® 1000

95th percentile

5


o Indications for the test Allergic conditions when allergen is suspected and mentioned on request

o Factors affecting the test Total IgE >3000kIU/increases the incidence of false positive low level specific IgE. IgE <30 kIU/l associated with false negative specific IgE

Clinical workstation reference: ALLERGENS Allergen Specific IgE

Department of



Amphiphysin Referred to: Department of Immunology

Salford Royal Hospital Stott Lane Salford M6 8HD

General Information


o Special precautions:


Normal Reference

Range


Method

Turnaround time


Median 16 Negative

7 ml clotted blood

Western Blot 95th

percentile 34


o Indications for the test


Department of



Anti-Basal Ganglia Abs Referred to: Institute of Neurology National Hospital for Neurology and Neurosurgery Queens Square London WC1N 3BG General Information




Normal Reference

Range


Method

Turnaround time


Median 16 Negative

7 ml clotted blood

Western Blot 95th

percentile 34




Department of



Anti C1q Referred to: Department of Immunology


General Information




Normal Reference

Range


Method

Turnaround time


Median 16 <15 U/ml

7 ml clotted blood

EIA 95th

percentile 34


o Indications for the test HUV, SLE with renal involvement o Factors affecting the test

Department of



Anti-Neutrophil cytoplasmic antibody (ANCA) General Information Anti-neutrophil cytoplasmic antibodies (ANCA) are found in several types of

vasculitis. Samples for ANCA are initially tested by immunofluorescence on neutrophils. Positive samples are then further tested by multiplex flow immunoassay for specific antibodies against either proteinase 3 (PR3) or myeloperoxidase (MPO). In general, a classical c-ANCA pattern corresponds to PR3 reactivity whilst a perinuclear p-ANCA pattern corresponds to MPO reactivity. Atypical ANCA patterns do not usually correspond to either antigen.

These tests are used to diagnose vasculitis and to monitor disease activity. Infections and autoimmunity can produce false positive tests reducing the specificity of ANCA testing.

o Specimen transport: At room temperature o Repeat Frequency: No more frequently than every four weeks,

except when plasmapheresis is being done.

o Special precautions: None Laboratory Information

Normal

Reference Range


Method

Turnaround time (calendar days from

sample receipt to authorised result)

Median 3 Neg

7 ml clotted

blood


percentile 7

WE WILL UNDERTAKE URGENT SAME DAY TESTING DURING LABORATORY OPENING HOURS PROVIDED THAT THE LABORATORY IS CONTACTED BY PHONE AND THE SAMPLE ARRIVES BEFORE NOON. Clinical Information

o Indications for the test ANCA testing is helpful in patients with vasculitis affecting the kidneys

o Factors affecting the test Positive ANA i.e. the presence of other autoantibodies False positives see in infections.

Guidelines are provided in the following reference: Addendum to the International Consensus Statement on Testing and reporting

of ANCA Am J Clin Pathol 2003; 120; 312-318 Clinical workstation reference: ANCA Neutrophil cytoplasmic Ab (ANCA)

Department of



Antinuclear antibody (ANA), includes anti-centromere

General Information “Antinuclear antibody” refers to an old test for IgG against nuclear

components, detected by immunofluorescence. This test has been superseded by faster, more reproducible parallel tests for each of the nuclear components, namely ENA (extractable nuclear antigens SS-A (SS-A52, SS-A60) (Ro), SS-B (La), Sm, Sm/RNP, RNP (RNPA, RNP 68), Ribo P, Chromatin, Jo-1 and Scl70), DNA and centromeres. When you request ANA we will perform the above tests; if any are positive this will be indicated as a positive ANA. If the specificity of the positive ANA is not indicated, please note that the laboratory can release this extra information if you contact us within 2 weeks of the original specimen receipt.

Please see also ENA, DNA and centromere antibodies.

o Specimen transport: At room temperature o Repeat Frequency: On appearance of new symptoms



Normal Reference

Range


Method

Turnaround time


Median 1 ANA – Neg Centromere <0.9AI

7 ml clotted

blood

Multiplex flow Immunoassay

95th percentile

4


o Indications for the test Suspected SLE, connective tissue disease, hepatitis or drug induced lupus.

o Factors affecting the test May be positive due to the age of the patient or due to infection. For these reasons positive results have a low predictive value in the absence of clinical signs of the diseases indicated above. ANA

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should not, therefore, be used as a “screen” in patients with vague symptoms and signs.

Clinical workstation reference: ANA Antinuclear antibody (includes anti-centromere)

Department of



Aquaporin 4 / NMO (Neuro Myelitis Optica Abs) Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ General Information




Normal

Reference Range


Method



Median 16 Negative

7 ml clotted

blood

Immunofluorescence

95th percentile

34


o Indications for the test o Factors affecting the test

Department of



Aspergillus fumigatus precipitins General Information Precipitin Testing: These tests detect the presence of IgG antibodies to Aspergillus fumigatus, Aspergillus precipitins – see also: Farmer’s lung and Avian Precipitins




Normal Reference

Range


Method

Turnaround time


Median 1 0-40 mg/l

7 ml clotted

blood

FEIA

(Fluoroenzyme immunoassay)

95th percentile

5


o Indications for the test Allergic bronchopulmonary aspergillosis – IgG antibodies are a useful aid to diagnosis in the following settings: Bronchopulmonary aspergillosis; usually presents as deteriorating or brittle asthma. IgE antibodies should also be checked. Aspergilloma; these may form in cavities or bronchiectatic lung. For example, this test is used to check for aspergilloma in patients with cystic fibrosis. Hypersensitivity pneumonitis 24 hours after inhalation of spores.

o Factors affecting the test Aspergillus antibodies are not a recommended test for the investigation of the majority of cases of invasive aspergillosis in immunocompromised hosts.

Department of



o Interpreting results IgG antibodies are infrequent in healthy individuals. In hypersensitivity pneumonitis, IgG antibodies are usually present alone. IgG antibodies, without IgE antibodies can also be seen in some cases of sub acute invasive aspergillus. In bronchopulmonary aspergillosis and aspergilloma a mixture of IgE and IgG antibodies are usually present. Bronchopulmonary aspergillosis can be caused by species other than A. fumigatus: if there is a high index of suspicion, we can send a sample to the reference laboratory to look for antibodies to other Aspergillus species. In allergic rhinitis and asthma, where aspergillus is a relevant allergen, IgE antibodies dominate.

Clinical workstation reference: ASPERGILLUS Aspergillus fumigatus precipitins

Department of



Avian precipitins General Information As for Aspergillus precipitins




Normal Reference

Range


Method

Turnaround time (calendar days from sample receipt to authorised result)

Median 1 0-40 mg/L

7 ml clotted

blood

FEIA

(Fluoroenzyme immunoassay)

95th percentile

5


o Indications for the test Respiratory symptoms associated with avian exposure


Positive results are seen in some healthy individuals exposed to birds.

Clinical workstation reference: AVIAN Avian precipitins

Department of



Bence Jones Protein (Urinary light chains) Urine immunofixation

General Information

o Specimen transport: Specimen should ideally be sent fresh o Repeat Frequency:



Normal Reference

Range


Method


Median 3 Absent

20 ml urine

Immunofixation 95th

percentile 6


o Indications for the test Suspected myeloma, Waldenström’s macroglobulinaemia, rarely lymphoma.


24 hour urine is more sensitive. Polyclonal free light chains may be found with renal tubular damage, old age, chronic inflammatory conditions (like RA). Monoclonal light chains may also be found associated with prostatic problems in older men.

Clinical workstation reference: BENCE JONES Bence Jones protein

Department of



ß2 Microglobulin

General Information High levels are seen in myeloma




Normal Reference

Range


Method


Median 2 <3 mg/L

7 ml clotted

blood

Nephelometry 95th

percentile 17


o Indications for the test Useful for monitoring turnover in myeloma and lymphoma


Elevated levels are associated with renal impairment Chronic dialysis

Clinical workstation reference: B2M ß2 Microglobulin

Department of



Centromere antibody – refer to ANA panel General Information Centromere antibody is detected as part of our ANA panel. Centromere is

seen in limited systemic sclerosis (CREST syndrome – calcinosis, Raynaud’s, oesophageal dysmotility and telangiectasia) and in primary biliary cirrhosis.




Normal Reference

Range


Method


Median 1 <0.9 AI

7 ml clotted

blood

Multiplex flow immunoassay

95th percentile

4




Clinical workstation reference: ANA Antinuclear antibodies

Department of



C1 esterase inhibitor General Information Should always request C4 at the same time




Normal Reference

Range


Method



Median 2 0.21 – 0.5 g/l (21-50 mg/dl)

7 ml clotted

blood

Single radial

immunodiffusion 95th percentile

17


o Indications for the test Suspected type I hereditary angioedema. This disease causes recurrent attacks of abdominal pain or swellings. The complement component C4 is almost always low in HAE. This is used as a reliable screen for the disease.


Clinical workstation reference: C1 INH and C4 C1 esterase inhibitor

Department of



C1 esterase inhibitor functional test

General Information

o Specimen transport: All samples from outside the hospital should be transported on an ice pack. Transport at room temperature is acceptable within this hospital if the sample is delivered to the Immunology Laboratory within 3 hours.

o Repeat Frequency:



Normal Reference

Range


Method


Median

2 70 – 140

% Normal

5 ml sodium citrate blood

Enzyme

immunoassay 95th percentile

17


o Indications for the test Angioedema associated with low C4 when C1-esterase inhibitor is normal or high.


Also seen in acquired C1-inhibitor deficiency in older patients where it is associated with myeloma/lymphoma.

Clinical workstation reference: C1 INH FUNC C1 esterase inhibitor functional test

Department of



C1q Referred to: Department of Immunology


General Information




Normal Reference

Range


Method


Median 16 50-250 mg/l

7 ml clotted blood

RID 95th

percentile 34


o Indications for the test Levels are reduced in acquired angioedema Levels are also reduced in urticarial vasculitis – a complication of SLE Sjögren’s syndrome, cryoglobulinaemia and hepatitis C infection o Factors affecting the test

Clinical workstation reference: C1Q C1q

Department of



C3 nephritic factor

Referred to: Department of Immunology


General Information




Normal Reference

Range


Method


Median 16 Negative

7 ml clotted

blood

Electrophoresis 95th

percentile 34


o Indications for the test Mesangiocapilliary glomerulonephritis, only performed if C3 is low <0.3 g/l


-

Clinical workstation reference: C3 NEF C3 nephritic factor

Department of



Cardiac muscle antibodies General Information Associated with Dressler’s syndrome




Normal

Reference Range


Method



Median 3 Neg

7 ml clotted

blood


percentile 10


o Indications for the test Dressler’s syndrome (after M.I. post-cardiac surgery, some cardiomyopathies and following acute rheumatic fever).


Clinical workstation reference: HEART Ab to cardiac muscle

Department of



Cardiolipin (IgG and IgM) antibodies General Information Found in the anti-phospholipid syndrome, which may be primary or occur as a secondary complication of SLE. Elevated levels are significantly associated with the presence of both venous and arterial thrombosis, thrombocytopaenia, and recurrent fetal loss.

o Specimen transport: At room temperature o Repeat Frequency: Cardiolipin antibodies are transiently

positive in many infections. British Society for Standards Clinical Haematology guidelines require two positive tests; cardiolipin or lupus anticoagulant with a 12 week interval, to diagnose antiphospholipid syndrome.



Normal Reference

Range


Method


Median 1 IgG 0-5.6 GPLU/mlIgM 0-10 GPLU/ml

7 ml clotted blood

FEIA

95th percentile

4

Borderline Results: IgG 5.7-8.0 GPLU/ml IgM 10-12.0 GPLU/ml Borderline results should be repeated if high clinical index of suspicion of anti-phospholipid syndrome. Clinical Information

o Indications for the test Thrombosis, miscarriage


False positives in infections

Clinical workstation reference: CARDIOLIPIN Ab to cardiolipin (IgG and IgM)

Department of



Anti-Cyclic citrullinated peptide (CCP)

General Information




Normal Reference

Range


Method


Median 1 0-10 U/ml

7 ml clotted blood

FEIA 95th

percentile 4


o Indications for the test CCP antibodies are targeted against citrullinated peptides are highly specific to rheumatoid arthritis (RA) but may also be of value in the development of radiographic joint damage. CCP antibodies are implicated in the early diagnosis of RA and offer a marker that is more specific than Rheumatoid Factor.


Clinical workstation reference:

Department of



CD34 (Stem cells) General Information

o Specimen transport: At room temperature o Repeat Frequency: Each day or stem cell harvest



Normal Reference

Range


Method


Median 2 Percentage and absolute counts

Peripheral blood stem cell harvest

or 5 mls bone marrow in heparin and tissue culture

medium

Flow cytometry

95th percentile

3


o Indications for the test -


-

Clinical workstation reference: CD34 CD34 (Stem cells)

Department of



CD3 (T cells) General Information

o Specimen transport: At room temperature o Repeat Frequency: Daily during treatment with ATG



Normal Reference

Range


Method


Median 2 Percentage and absolute counts

5 mls EDTA

blood

Flow cytometry

95th percentile

7


o Indications for the test Patients on ATG As part of lymphoma panel


-

Clinical workstation reference: CD3 CD3 (T cells)

Department of



CD4 count (T cell count) (for patients with known HIV serology)

General Information The CD4 count is used to monitor disease progression in HIV infection. For example, patients with counts below 200 x 106/L are at risk of pneumocystis pneumonia and should received antibiotic prophylaxis. CD4 counts are also used to inform decision making on anti-retroviral therapy. BHIVA publish guidelines on CD4 counts and their interpretation: - www.aidsmap.com Apart from HIV infection, the CD4 count can be reduced by acute and chronic stress, including infections and physical or psychological stress. CD4 counts are also affected by daily circadian rhythms and the menstrual cycle.

o Specimen transport: An EDTA specimen should arrive in the lab on the same day or within 48 hours maximum. Samples should be stored and transported at room temperature and not refrigerated.

o Repeat Frequency: Three times a year in asymptomatic patients,

more frequently in those with symptoms or when medication is being changed.



Normal Reference

Range


Method


Median 1 Absolute counts

provided 500-1500x106/L

5 ml EDTA blood

Flow cytometry – single platform 95th

percentile 3

Clinical Information o Indications for the test For use as a monitoring tool in serologically confirmed HIV infection. Should not be used in an attempt to diagnose HIV infection.

o Factors affecting the test Because physiological stress can affect results, avoid testing during acute infections, postoperatively etc. Always try and do monitoring tests at the same time of day. In women, try to do monitoring tests at the same phase of the menstrual cycle.

Clinical workstation reference: CD4 CD4 count (T cells)

Department of



CH100 complement activity Classical Pathway

General Information

o Specimen transport: Sample required on ice pack o Repeat Frequency:

o Special precautions: Transport as soon as possible to lab.


Normal Reference

Range


Method


Median 6 Age and gender

specific

7 ml EDTA blood

on ice

Timed lysis

95th percentile

14

Age and gender specific normal ranges

Test Units 0 days – 4 weeks

4 weeks – 12

years

12-20 years

20-50 years

50 – 90+ years

CH100

% normal

50-140

60-160

80-160

M80-180 F70-200

80-180


o Indications for the test Suspected complement deficiency eg. meningococcal infection


If screened too soon after acute infection leads to false (positive) results

Clinical workstation reference: CH50 CH50 complement activity Classical Pathway

Department of



Chronic lymphocytic malignancies/lymphoma panel General Information Panel of markers used: CD3, CD5, CD19, CD23, CD79b, Kappa chains, Lambda

chains, FMC7, CD38

o Specimen transport: At room temperature in EDTA tube. Marrow, lymph node aspirate and lymph node should be placed in tubes containing special medium (provided by the laboratory)

o Repeat Frequency:

o Special precautions: Do not refrigerate


Normal Reference

Range


Method



10 mls EDTA

blood or 5 mls bone marrow in

heparin with transport medium

Flow cytometry

95th percentile

7




Clinical workstation reference: CHRONIC Chronic lymphocytic malignancies/lymphoma panel

Department of



Complement C3 General Information




Normal Reference

Range


Method


Median 1 Age and gender specific normal

range

7 ml clotted

blood

Nephelometry

95th percentile

5

Age and gender specific normal ranges

Test Units 0 days – 4 weeks

4 weeks – 12 years

12-20 years

20-50 years

50 – 90+ years

C3

g/l

0.32-1.4

0.62-1.6

M0.62-1.2 F0.62-1.5

0.62-1.6

0.62-1.6


o Indications for the test Monitoring of SLE. Post streptococcal glomerulonephritis and other conditions of complement activation.


Traumatic venepuncture or delay in transport may lead to falsely low levels.

Clinical workstation reference: C3 Complement C3

Department of



Complement C4 General Information Useful in monitoring a wide range of inflammatory and autoimmune disorders.

Single point determinations are of limited value and serial measurements are recommended.




Normal Reference

Range


Method


Median 1 0.14-0.43 g/l

7 ml clotted

blood

Nephelometry 95th

percentile 5


o Indications for the test Pre-eclampsia, hereditary angioedema, genetic deficiency, active SLE (associated with low C3) sepsis (associated with low C3).

o Factors affecting the test Traumatic venepuncture and delay in transport can lead to false negative results due to in vitro activation.

Clinical workstation reference: C4 Complement C4

Department of



Crithidia antibodies General Information Used for the detection of antibodies that are specific for double stranded DNA

o Specimen transport: At room temperature o Repeat Frequency: Only on change of clinical allergy

o Special precautions: none


Normal

Reference Range


Method



Median 6 Neg

7 ml clotted

blood


percentile 13




Clinical workstation reference: not applicable Ab to crithidia

Department of



Cryoglobulins General Information

o Specimen transport: Sample in Thermos at 37o C Contact the laboratory to arrange

collection of the Thermos flask o Repeat Frequency:

o Special precautions: The sample must be taken into a pre-

warmed syringe and then pre-warmed tubes. It must be transported at 37o C in a Thermos flask. Always contact the laboratory before bleeding the patient.


Normal

Reference Range


Method



Median 4 Not normally

detected

7 ml clotted blood maintained at 37o

C

Immunofixation

95th percentile

8


o Indications for the test Lymphoproliferative disease (Monoclonal) Connective tissue disease: SLE, Sjogren’s, Raynaud’s and cutaneous vasculitis. There is almost always a low C4 in cryoglobulinaemia

o Factors affecting the test Any minor variations in temperature (1o C)

Clinical workstation reference: CRYOGLOBULINS Cryoglobulins

Department of



Double stranded DNA antibodies (IgG) General Information The presence of autoantibodies to double stranded DNA is strongly suggestive

of SLE, although they are detected in only 40-60% of patients with this disease.

o Specimen transport: At room temperature o Repeat Frequency: We recommend not repeating this test more

than once a month, unless the patient is undergoing plasmapheresis



Normal

Reference Range


Method



Median 1 <13.9 IU/ml

7 ml clotted

blood

Multiplex flow immunoassay and

Immunofluorescence95th

percentile 5


o Indications for the test Diagnosis and monitoring of lupus

o Factors affecting the test We use two assays to detect DNA antibodies:

- Crithidia is a source of pure double stranded DNA and gives a qualitative result.

- The multiplex assay can be contaminated by single stranded DNA, but gives quantitative results.

o The following configurations can be seen:

- Crithidia Positive + multiplex flow immunoassay positive = indicates active lupus

- Crithidia Negative + multiplex flow immunoassay positive = indicates single stranded DNA antibodies, usually triggered by infection or drugs.

Clinical workstation reference: DNA Ab to double stranded DNA (IgG)

Department of



ENA antibodies – includes Ro (SS-A), La (SS-B), Sm/RNP, RNP, Jo-1, Scl-70 General Information Antibodies to extractable nuclear antigens are of use in the classification of

clinical subsets of connective tissue diseases and in providing prognostic information.

o Specimen transport: At room temperature o Repeat Frequency: Not more than once a year, if clinical

picture has changed

o Special precautions: Laboratory Information

Normal Reference

Range


Method


Median 1 <0.9 AI

7 ml clotted

blood


95th percentile

4


o Indications for the test Anti-Ro (SS-A) SLE, Sjögren’s syndrome, neonatal lupus In pregnancy it may cause congenital defects Anti-La (SS-B) SLE, Sjögren’s syndrome, neonatal lupus Anti-RNP SLE, Mixed connective tissue disease Anti-Scl 70 Progressive systemic sclerosis (generalised scleroderma) Anti-Jo-1 Polymyositis, Dermatomyositis


Clinical workstation reference: ENA Ab to ENA panel

Department of



IgA Anti-Tissue Transglutaminase General Information Acts as a screening test for coeliac disease/dermatitis herpetiformis

o Specimen transport: At room temperature o Repeat Frequency: Only to monitor compliance with

gluten free diet


Normal Reference

Range


Method


Median 1 0-6.9 U/ml

7 ml clotted blood

FEIA 95th

percentile 4


o Indications for the test Suspected gluten sensitivity. This test is specific for coeliac disease, but a jejunal biopsy is recommended for confirmation.


Becomes negative on gluten free diet False Negative in IgA deficiency – our test platform will detect a low IgA level


Department of



IgG Anti-Tissue Transglutaminase General Information Acts as a screening test for coeliac disease/dermatitis herpetiformis

o Specimen transport: At room temperature o Repeat Frequency: Only to monitor compliance with

gluten free diet in IgA deficient patients



Normal Reference

Range


Method


Median 1 0-6.9 U/ml

7 ml clotted blood

FEIA 95th

percentile 4


o Indications for the test Suspected gluten sensitivity. This test is specific for coeliac disease, but a jejunal biopsy is recommended for confirmation.


Becomes negative on gluten free diet


Department of



Farmer’s lung precipitins General Information These tests detect the presence of IgG antibodies to Micropolysporium faeni

(Farmer’s lung precipitins).




Normal Reference

Range


Method


Median 1 0-60 mg/L

7 ml clotted blood

FEIA 95th

percentile 5


o Indications for the test Hypersensitivity to Micropolysporium faeni is a common cause of Farmer’s lung, hypersensitivity pneumonitis occurring 12 to 24 hours after exposure to mouldy hay.


In some cases of farmer’s lung, hypersensitivity to other fungal species may be implicated. The absence of IgG to Micropolysporium faeni does not rule the diagnosis out. These antibodies can be found in some healthy individuals. The presence of these antibodies supports, but does not confirm, a diagnosis of farmer’s lung. There are numerous other causes of hypersensitivity pneumonitis including other fungal spores and occupational antigens. Please discuss with the laboratory if these may be incriminated.

Clinical workstation reference: FARMER’S LUNG Farmer’s lung precipitins

Department of



Free Light Chains General Information This test measures immunoglobulin light chains not incorporated into intact

immunoglobulin molecules. Serum levels are increased when production is increased (myeloma) or excretion is impaired (renal failure)




Normal Reference

Range


Method


Median 3 Ratio 0.26-1.65 Free κ = 3.30-

19.40 mg/L Free λ = 5.7-26.30

mg/L

7 ml clotted

blood

Nephelometry

95th percentile

6


o Indications for the test May be used as part of the diagnostic strategy for myeloma. This test has largely superseded Bence Jones protein (urine immunofixation). Monitoring in some cases of myeloma.



Department of



Gamma Interferon (Quantiferon) General Information This test measures gamma interferon produced by T cells in response to mycobacterial peptides

o Specimen transport: Samples should reach the laboratory within 4 hour of being drawn. The test is not performed on Fridays. An alternative for hospitals outside Greater Manchester is to incubate the samples locally, centrifuge them and send the supernatant. This should only be done after discussion with laboratory staff.

o Repeat Frequency:

o Special precautions: Three special sample tubes are required for

this test. They can be obtained from Immunology. These tubes are vacutainer and will draw 1 ml of blood. Please do not take the caps off the tubes. Please do not overfill the tubes.


Normal Reference

Range


Method


Median 7 Neg

The test requires special sample

tubes obtainable from Immunology

(x66440)

ELISA

95th percentile

11


o Indications for the test The test is used to help diagnose latent TB infection and is indicated in individuals with a positive delayed hypersensitivity skin test.

o Factors affecting the test The test is less reliable on patients with suspected active TB (as opposed to latent TB), infants and in immune deficiency states.

Clinical workstation reference: None Gamma Interferon (Quantiferon)

Department of



Ganglioside Abs GM1

Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 0-200 titre

7 ml clotted blood

ELISA 95th

percentile 34


o Indications for the test Guillian-barre syndrome, chronic demyelinating polyneuropathy Multifocal motor neuropathy


Clinical workstation reference: GM1 IgM Ab to ganglioside GM1

Department of



Ganglioside Abs GQ1b Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 0-25 titre

7 ml clotted blood

ELISA 95th

percentile 34



Miller-Fisher Syndrome


Department of



Glomerular basement membrane antibodies General Information Diagnostic test for Goodpasture’s syndrome




Normal Reference

Range


Method


Median 1 <0.9 AI

7 ml clotted

blood

Multiplex Flow Immunoassay

95th percentile

4


o Indications for the test Rapidly progressive glomerulonephritis.


In comparison to biopsy proven cases of GBM disease, ELISA tests for anti-GBM antibodies have been shown to have a clinical diagnosis agreement of 97%, a sensitivity of 87% and a specificity of 98%. A small number of patients with other renal diseases – systemic vasculitis, SLE and mixed connective tissue disease may exhibit borderline titres.

Clinical workstation reference: GBM Ab to glomerular basement membrane (GBM)

Department of



Glutamic Acid Decarboxalase Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 0-1 U/ml

7 ml clotted blood

RIA 95th

percentile 34



IDDM, Stiff-man syndrome


Department of



Histone Abs Referred to: Department of Immunology


General Information




Normal Reference

Range


Method


Median 16 <40 U/ml

7 ml clotted blood

EIA 95th

percentile 34



Drug-induced SLE. Also positive in RA/SLE etc.


Department of



IgE (Total) General Information




Normal Reference

Range


Method


Median 2 Age specific

7 ml clotted

blood 14 ml if multiple

tests

Immunoassay (Immunocap®

1000) 95th

percentile 5

Age Total IgE kU/L Age Total IgE kU/L 0 – 2 days 0.1- 1 8 – 12 years 0.1- 100 3 days- 2 weeks 0.1- 2 12 – 16 years M 0.1- 400 2 – 4 weeks 0.1- 6 12- 16 years F 0.1- 340 4 – 8 weeks 0.1- 10 16- 20 years M 0.1- 400 8 weeks – 3 months 0.1- 20 16 – 20 years F 0.1- 300 3 – 6 months 0.1- 30 20 – 40 years 0.1- 200 6 – 12 months 0.1- 40 40 – 50 years 0.1- 150 1 - 4 years 0.1- 50 50 – 70 years 0.1- 100 4 – 8 years 0.1- 60 70 – 90+ years 0.1- 80 Clinical Information

o Indications for the test Patients with suspected allergy (atopic disease). Main use of the test is to help interpret specific IgE levels.

o Factors affecting the test Sensitivity of specific IgE is low when total IgE <50 kIU/L Specificity, at low levels of specific IgE, is low when total IgE >3000 kIU/l

Clinical workstation reference: IgE IgE (Total)

Department of



IgG subclasses General Information - IgG1,2,3,4

o Specimen transport: At room temperature o Repeat Frequency: Not within 6 months



Normal Reference

Range


Method



specific

7 ml clotted

blood

Nephelometry

95th percentile

5

Age IgG1 g/l IgG2 g/l IgG3 g/l IgG4 g/l 0-1 days 2.9 – 12.6 1.1 – 6.6 0.2 – 1.4 0.05 – 1.4 1-2 days 2.7 – 14.6 1.1 – 6.9 0.2 – 1.2 0.04 – 1.3 3-6 days 2.4 – 11.6 <1 - 6.4 0.2 – 1.0 0.04 – 1.2 1-2 weeks 2.1 – 10.8 0.7 – 4.9 0.1 – 0.8 0.03 – 0.9 2-4 weeks 1.9 – 9.8 0.5 – 2.9 0.1 – 0.8 0.02 – 0.7 4-8 weeks 1.4 – 8.8 0.3 – 2.6 0.1 – 0.8 0.02 – 0.5 8-16 weeks 1.2 – 8.8 0.3 – 2.6 0.1 - <1 0.02 – 0.3 16-26 weeks 1.6 – 9.8 0.4 – 2.3 0.1 - <1 0.03 – 0.7 6-12 months 1.8 – 10.8 0.5 – 2.3 0.1 – 1.2 0.02 – 1.4 1-4 years 2.4 – 12.6 0.6 – 2.6 0.2 – 1.4 0.02 – 1.8 4-8 years 3.4 – 14.6 0.6 – 2.9 0.2 – 1.3 0.02 – 1.8 8-12 years 3.4 – 11.6 0.7 – 4.4 0.2 – 2.9 0.02 – 1.8 12-16 years 3.4 – 11.6 0.8 – 7.8 0.2 – 2.8 0.03 - 3 16-20 years 3.4 – 11.6 1.1 – 6.6 0.2–2.0 (0.2-

1.3) 0.05 – 2

20-40 years 2.9 – 12.6 1.1 – 6.6 0.2 – 1.3 0.05 – 2 40-50 years 2.9 – 12.6 1.1 – 6.6 0.2 – 1.3 0.05 – 2 50-70 years 2.9 – 12.6 1.1 – 6.6 0.2 – 1.3 0.05 – 2 70-90+ years 3.9 – 13.6 1.1 – 6.6 0.2 – 1.3 0.05 - 2 Clinical Information

o Indications for the test History of bacterial sinopulmonary infection and IgG between 5-16 g/l History of/or failure to respond to polysaccharide vaccines, pancreatitis (history of recurrent infections – not viral), or abscesses or (failure to respond to immunisation) AND (Total IgG < 0.1 g/l). Samples not meeting these requirements will be rejected.

Department of



o Factors affecting the test Clinical workstation reference: IGG SUBCLASS IgG subclasses

Department of



Immunodeficiency (Contact on 0161 276 6440 to discuss extended panels for investigation of Primary Immunodeficiency)

General Information These tests are most frequently done in patients receiving immunosuppressive drugs. For example, cyclosporine reduces T cell numbers, whilst Rituximab reduces B cell numbers. The relevant tests required will be specified for each individual case.

o Specimen transport: All cellular tests at room temperature o Repeat Frequency:



Normal Reference

Range


Method


Median 2 Absolute counts

EDTA (7 mls)

blood

Flow Cytometry 95th

percentile 7


o Indications for the test Suspected cellular immunodeficiency


Clinical workstation reference: IMMUNODEF Immunodeficiency

Department of



Immunoglobulins (IgG, IgA, IgM) General Information IgA: raised in elderly, chronic infection, cirrhotic liver disease IgM: raised primary biliary cirrhosis, acute infection, EBV, CMV, TB Marked polyclonal IgG elevation is seen in HIV, Sjögren’s, and Sarcoidosis Less marked elevation in chronic inflammatory and infective conditions.

o Specimen transport: At room temperature o Repeat Frequency: Not within six months – exempt for

monitoring myeloma and immunodeficiency


Normal Reference

Range


Method



specific

7 ml clotted

blood

Nephelometry

95th percentile

5

Age and gender specific reference ranges for total serum IgG, IgA and IgM Age IgG IgA IgM M Age IgG IgA IgM g/l g/l g/l F g/l g/l g/l 0-1 day

5.9-15.6

0-0.10 0-0.2 1-4 yrs 4.9-15.6

0.3-2.0 0.4-1.9

1-2 days

5.4-14.6

0-0.10 0.10-0.2 4-8 yrs 5.9-15.6

0.4-2.5 0.4-2.9

3-6 days

4.9-13.6

0-0.10 0.10-0.3 8-12 yrs 5.9-15.6

0.6-3.0 0.5-2.9

1-2 wks

3.9-11.6

0-0.2 0.10-0.5 M F

12-16 yrs 6.4-16 5.9-15.6

0.7-4.0 0.6-4.0

0.4-2.3 0.6-2.9

2-4 wks

2.9-9.8 0.10-0.3 0.2-0.6 M F

16-20 yrs 6.4-16.0

0.7-4.0 0.4-2.3 0.7-3.4

4-8 wks

2.4-9.8 0.10-0.4 0.2-0.8 M F

20-40 yrs 5.9-15.6

0.6-5.0 0.4-2.4 0.6-3.4

8-12 wks

1.9-9.8 0.10-0.5 0.2-1.4 M F

40-50 yrs 5.9-15.6

0.6-5.0 0.4-2.3 0.6-3.4

12-26 wks

2.4-10.8

0.10-0.6 0.3-1.9 M F

50-70 yrs 5.9-15.6

0.6-5.0 0.4-2.3 0.6-2.9

6-12 mths

3.9-11.6

0.2-1.0 0.3-1.9 M F

70-90+ yrs

5.9-15.6

0.6-4.0 0.4-2.3 0.5-2.4

Department of




o Indications for the test 1. Recurrent infections 2. Suspected myeloma, Waldenstrom’s macroglobulinaemia,

lymphoma, connective tissue disease.


Age, primary/secondary immunodeficiency

Clinical workstation reference: IGS and EP IgG, IgA, IgM, electrophoresis

Department of



Immunoglobulin D, IgD Referred to: Department of Immunology


General Information




Normal Reference

Range


Method


Median 16 2-100 KU/L

7 ml clotted blood

EIA 95th

percentile 34



Familial Mediterranean Fever


Department of



Immunophenotyping for lymphoid and myeloid malignancies (full clinical details required) General Information Cell surface markers appropriate to diagnostic information provided The relevant tests required will be specified for each individual case.

o Specimen transport: Bone marrow (see below) at room temperature

Peripheral blood (see below) at room temperature

o Repeat Frequency:



Reporting Units


Method



10 ml EDTA

blood or 5 ml bone marrow in

heparin with tissue culture

medium

Flow Cytometry

95th percentile

7

* Blood markers: Percentage lymphocytes, mononuclear or nucleated cells Bone marrow markers: Percentage lymphocytes, mononuclear or nucleated cells Clinical Information

o Indications for the test Suspected lymphoid/myeloid malignancy To confirm relapse To confirm remission

o Factors affecting the test Specimens should be ideally <24 hours old and never more than 48 hours old

Clinical workstation reference: IMMUNOPHEN Immunophenotyping for lymphoid and myeloid malignancies

Department of



Insulin Antibodies Referred to: SAS Laboratory The Royal Guilford County Hospital Egerton Road Guilford Surrey GU2 7XX

General Information




Normal Reference

Range


Method


Median 16 Negative

7 ml clotted blood

ELISA 95th

percentile 34


o Indications for the test Insulin resistance


-

Department of



Islet Cell Antibodies General Information Predictive of future insulin requirement in patients presenting with NIDDM* and in relatives of IDDM* patients.




Normal

Reference Range


Method



Median 3 Neg

7 ml clotted

blood


percentile 11


o Indications for the test Screening of first degree relatives for risk of developing insulin dependent diabetes mellitus. May also be used to determine the risk of IDDM in gestational diabetes


Detectable within first year after diagnosis in IDDM patients

* NIDDM Non-insulin dependent diabetes mellitus * IDDM Insulin dependent diabetes mellitus Clinical workstation reference: ISLET CELL Ab to islet cells

Department of



Mannose Binding Lectins Referred to: Immunology Department Camelia Botnar Laboratories Level 4 Great Ormond Street Hospital London WC1N 3JH

General Information




Normal Reference

Range


Method


Median 16 0-1300ng/ml

7 ml clotted blood

ELISA 95th

percentile 34


o Indications for the test Recurrent infections in childhood


Department of



Muscle Specific Tyrosine Kinase (MUSK)

Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 Negative

7 ml clotted blood

RIA 95th

percentile 34




Department of



Myelin Associated Glycoprotein (MAG) Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 Neg

= <1000 BTU (Boulman Time

Unit)

7 ml clotted blood

ELISA

95th percentile

34


o Indications for the test IgM monoclonal neuropathy


Department of



Myeloperoxidase (MPO) antibodies

General Information Autoantibodies to myeloperoxidase are found in the sera of patients with various types of systemic vasculitis including (idiopathic crescentic glomerulonephritis), Churg-Strauss syndrome, microscopic polyangiitis and polyartheritis nodosa.

o Specimen transport: At room temperature o Repeat Frequency: Used to monitor response to treatment



Normal Range


Method


Median 1 <0.9 AI

7 mls clotted

blood

Multiplex Flow Immunoassay

95th percentile

8


o Indications for the test Investigation of patients with systemic vasculitis


Clinical workstation reference: MPO Ab to myeloperoxidase MPO (p-ANCA)

Department of



Mast Cell Tryptase

General Information

o Specimen transport: At room temperature o Repeat Frequency: For suspected anaphylaxis as soon as

possible (within 3 hrs) after the patients condition has been stabilized after the reaction, and repeat at 6 and 24 hours

For mastocytosis repeat after 1 year or following significant clinical change

o Special precautions: For suspected anaphylaxis the first

sample should be obtained as soon as possible after the patient’s condition has been stabilised.


Normal Reference

Range


Method


Median 1 0-12.9 ug/L

7 ml clotted blood within 2 hours of

anaphylaxis

FEIA

95th percentile

4


o Indications for the test Suspected acute allergic reactions, suspected mastocytosis


Tryptase levels decline following an adverse reaction. The decline in tryptase levels can be confirmed providing that two blood samples are obtained (each indicating the time it was taken). 40% of the Manchester populations is alpha tryptase deficient. This may affect the normal range but future research is needed.

Clinical workstation reference: TRYPTASE Mast Cell Tryptase

Department of



Neonatal IgG

General Information

o Specimen transport: At room temperature or on ice pack o Repeat Frequency:



Normal Reference

Range


Method


Median 2 See age related

reference ranges

1 ml clotted

blood

Nephelometry

95th percentile

5


o Indications for the test “TORCH” group of infections


Transient neonatal hypogammaglobulinaemia

Clinical workstation reference: NEONATAL Neonatal IgG IgM

Department of



Ovary antibodies

General Information Autoantibodies to the ovary may interfere with fertility by masking functional proteins on the cell surface of ovarian cells or interfering with intracellular protein functions.




Normal

Reference Range


Method



Median 3 Neg

7 ml clotted

blood


percentile 9


o Indications for the test Suspected premature ovarian failure (15-50% of patients have positive antibodies)


Patients may also have adrenal and thyroid antibodies

Clinical workstation reference: OVARY Ab to Ovary

Department of



Paraneoplastic Antibodies (Hu, Yo, Ri) Referred to: Department of Immunology

Salford Royal Hospital Stott Lane Salford M6 8HD

General Information




Normal

Reference Range


Method



Median 16 Negative

7 ml clotted

blood

Immunofluorescence

and RAVO blot 95th

percentile 34




Department of



PR3 autoantibodies (cANCA)

General Information c-ANCA’s are directed to proteinase 3 and are typically associated with Wegener’s granulomatosis.

o Specimen transport: At room temperature o Repeat Frequency: Used to monitor response to treatment and

risk of relapse


Normal Range


Method


Median 1 <0.9 AI

7 ml clotted

blood


95th percentile

8


o Indications for the test Suspected Wegener’s granulomatosis and monitoring treatment


Sensitivity of 66% and specificity of 98%

Clinical workstation reference: PR3 Ab to proteinase 3 PR3 (c-ANCA)

Department of



Rheumatoid factor

General Information




Normal Reference

Range


Method


Median 1 < 20 units

7 ml clotted

blood

Nephelometry 95th

percentile 5


o Indications for the test Aid for the prognosis of RA and Sjögren’s syndrome in the presence of an erosive arthropathy. Rheumatoid factor is not useful in the diagnosis of rheumatoid arthritis, it has a limited role in predicting the risk of complications particularly vasculitis.

o Factors affecting the test Disease activity: only 70-80% of patients with confirmed RA have positive rheumatoid factor. Detected in 2-10% of general population. Elevated titres may also accompany a variety of acute immune responses particularly infections (50%), liver disease, Sarcoidosis, and SLE.

Clinical workstation reference: RH FACTOR Rheumatoid factor

Department of



Serum Paraprotein identification/quantification

General Information Additional information is provided under Serum Protein Electrophoresis and Bence Jones protein (Urine Immunofixation).

o Specimen transport: Serum and urine (ideally fresh) o Repeat Frequency:



Normal Reference

Range


Method



Median 5 Not applicable

7 mls clotted

blood

Electrophoresis+ Immunofixation

95th percentile

7


o Indications for the test Serum paraprotein quantitation or monitoring myeloma treatment


Clinical workstation reference: PARAPROTEIN Paraprotein identification/quantification

Department of



Serum Protein Electrophoresis (see IgG, IgA, IgM electrophoresis)

General Information




Normal Reference

Range


Method



Median 5 Not applicable

7 ml clotted

blood

Electrophoresis+ immunofixation

95th percentile

8




Fibrinogen in plasma sample or haemolysed sample

Clinical workstation reference: IGS AND EP Serum protein electrophoresis refer to: IgG, IgA, IgM, electrophoresis

Department of



Skin antibodies

General Information Two types of skin autoantibodies that detect different skin components are

recognised: - Intercellular cement substance (Pemphigus antibodies) - Basement membrane antibodies (Pemphigoid antibodies)

o Specimen transport: At room temperature o Repeat Frequency: Depending on changes in clinical picture



Normal

Reference Range


Method



Median 3 Neg

7 ml clotted

blood


percentile 8


o Indications for the test Bullous skin disorders, dermatitis herpetiformis


Clinical workstation reference: SKIN Ab to skin

Department of



Smooth muscle/mitochondrial antibodies (including liver kidney microsomal (LKM), gastric parietal cell (GPC), and ribosomal)

General Information Smooth muscle antibodies at a high titre are associated with chronic active hepatitis, and at low titres are more likely to be triggered by infection. Mitochondrial antibodies are associated with primary biliary cirrhosis.




Normal

Reference Range


Method



Median 3 Neg

7 ml clotted

blood


percentile 7


o Indications for the test Gastric parietal cells: Pernicious anaemia (PA), atrophic gastritis. Present in the early stages of PA, frequently diminish with disease progression. Ab to ribosomes (rRNP) Are associated with psychiatric symptoms of SLE (5-12% of patients) and may be found in RA.


Unable to determine gastric parietal cell antibodies in the presence of mitochondrial antibodies.

Clinical workstation reference: SM/MIT/LKM/GP Ab to Smooth muscle/mitochondria

Department of



Testis antibodies

General Information




Normal

Reference Range


Method



Median 3 Negative

7 ml clotted

blood


percentile 9





Department of



Thyroid peroxidase (TPO) antibodies

General Information TPO is the immuno-active microsomal antigen




Normal Reference

Range


Method


Median 1 0-59 IU/ml

7 ml clotted blood

FEIA 95th

percentile 5


o Indications for the test To identify an autoimmune cause for primary hypothyroidism. To identify the risk of progression to overt hypothyroidism in patients with borderline thyroid function tests. (For individuals with TSH excess or mild thyroid failure, a positive TPO antibody indicates an approximate two-fold increase in risk of progression to overt hypothyroidism). Prior to treatment with medication that may precipitate hypothyroidism. In pregnant women as a predictor of potential intrapartum hypothyroidism.


Present in high titre in 95% of patients with Hashimoto’s thyroiditis, some patient’s with Grave’s disease and primary myxoedema. Anti-TPO are also seen in 5-15% of normals but at low titre.

Clinical workstation reference: TPO Ab to thyroid peroxidase (TPO)

Department of



TSH Receptor Antibodies Referred to: Department of Immunology


General Information




Normal

Reference Range


Method



Median 16 Negative

7 ml clotted

blood

Chemiluminescence 95th

percentile 34


o Indications for the test Thyroid disorders/pregnancy/Grave’s disease. Risk of post-partum or neonatal thyroid dysfunction.


Department of



Voltage-Gated Calcium Channel Antibodies Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 0-45 pM

7 ml clotted blood

RIA 95th

percentile 34




Department of



Voltage-Gated Potassium Channel Antibodies Referred to: Department of Immunology The Churchill Hospital Old Road Headington Oxford OX3 7LJ

General Information




Normal Reference

Range


Method


Median 16 0-100 pM

7 ml clotted blood

RIA 95th

percentile 34




Department of



Information for Patients If you are a patient visiting this website, you may find the following links helpful. Allergy/Hypersensitivity National Asthma Campaign www.asthma.org.uk British Lung Foundation www.lunguk.org National Eczema Society www.eczema.org Anaphylaxis Campaign www.anaphylaxis.org.uk Coeliac Society www.coeliac.co.uk Organ Specific Autoimmunity Patient information www.niams.nih.gov/hi/topics/autoimmune Infection and Immunity UK Primary Immunodeficiency Network www.ukpin.org,uk Primary Immunodeficiency Association www.pia.org.uk Guidelines and information on CD4 counts www.aidsmap.com National Aids Trust www.nat.org.uk Terrence Higgins Trust www.tht.org.uk Malignancy British Committee for Standards in Haematology www.bschguidelines.com Leukaemia Research Fund www.lrf.org.uk Lymphoma associated www.lymphoma.org.uk Renal Disease National Kidney Federation www.kidney.org.uk Rheumatology/Connective Tissue Disease British Society for Rheumatology www.rheumatology.org.uk Lupus UK www.lupusuk.com Raynaud’s and Scleroderma Association www.raynauds.org.uk Arthritis Research Campaign www.arc.org.uk

http://www.lunguk.org/

http://www.eczema.org/

http://www.anaphylaxis.org.uk/

http://www.coeliac.co.uk/



http://www.nat.org.uk/

http://www.tht.org.uk/

http://www.lrf.org.uk/

http://www.lymphoma.org.uk/

http://www.lupusuk.com/

http://www.raynauds.org.uk/

http://www.arc.org.uk/

department of immunology - manchester university nhs ... · department of immunology ... immunology...

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