approach of primary immune deficiencies دکتر افشین شیرکانی فوق تخصص آسم و...
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![Page 1: Approach of Primary Immune Deficiencies دکتر افشین شیرکانی فوق تخصص آسم و آلرژی و بیماری های نقص ایمنی استادیار دانشگاه](https://reader035.vdocuments.mx/reader035/viewer/2022070403/56649f2e5503460f94c4818c/html5/thumbnails/1.jpg)
Approach ofPrimary Immune Deficiencies
شیرکانی افشین دکتر
ایمنی نقص های بیماری و آلرژی و آسم تخصص فوقدانشگاه استادیار
آمریکا ایمونولوژی و آلرژی و آسم آکادمی عضو
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Comparison of hypersensitivity reactions
reaction
Lymphocyte
Effector cells
Antibody Antigen Time Complement
Diseases
Type I B Eosinophils and basophils
IgE Allergen 15-20 min
- Asthma, atopic dermatitis urticaria
Type II B PMN IgM , IgG Surface Ag
? + Hemolytic disease of newborns
Type III
B PMN IgM, IgG Soluble Ag
6-8 h + SLE
Type IV
T Macrophages
- Intracellular Ag
24-72 h _ Tuberculosis
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Immunity Innate & Adaptive
• First line of defense• Nonspecific• Rapid onset• No protective
immunity• No memory• Phagocyte-
mediated
• Activated• Very specific• Slower• Protective immunity
possible• Memory possible• Lymphocyte-
mediated
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Definition
• Any defect in the integrity of the immune systems – It may be congenital or late onset– It may be inherited or non hereditary – It may be in innate or adaptive parts of immune
system
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Components of Immunity• Skin and mucosal barriers
• Innate immune system (nonspecific)–Phagocytic cells, NK cells, complement
• Adaptive immune system (specific)–T and B lymphocytes, antibodies
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Increasing susceptibility to infections
Increasing duration of infections
Increasing severity of infection
Continuous illness
Dependence to antibiotics
Infection with opportunistic agents
Unusual infection
Characteristics of infections
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Eight or more new ear infections within 1 year.
Recurrent, deep skin ororgan abscesses.
Two or more serious sinus infections within 1 year.
Persistent thrush in mouth orelsewhere on skin, after age 1.
Two or more months on antibiotics with little effect.
Need for intravenousantibiotics to clear infections.
Two or moredeep-seated infections.
A family history ofPrimary Immunodeficiency.
Two or more pneumonias within 1 year.
Failure of an infant to gainweight or grow normally.
The 10 Warning Signs Of Primary Immunodeficiency
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Primary Immunodeficiency
• B cell (Antibody ) system• T cell (cellular ) system• Phagocyte (PMN and mononuclear )• Complement
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Classification of Immunodeficiency
1. Humoral (B-cell) – quantitative or qualitative defects in antibody production account for more than 50% of defects.
2. Cellular (T-cell) – usually combined with humoral; account for 20-30%.
3. Phagocytic – defects in migration, or killing; account for ~18%.
4. Complement – account for ~2%
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About %40 of cases are diagnosed in the first year
Another %40 by age 5 years
Another %15 by age 16
Only %5 in adulthood
About %10 of registered cases are adults
Late-onset Patients exhibit CVID
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• Common Risk Factors for Frequent Infections– Day-care, school– Second-hand smoke– Atopy– Anatomic abnormalities including ciliary
defects– Retained foreign body– Gastroesophageal reflue– Cystic fibrosis
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Children referred for evaluation for immuno deficiency
%50 Turn out to be normal
%30 have allergy
%10 have a serious but nonimmunologic
disorder
Only %10 have an immunodeficiency
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Allergic disorders in contrast to immunodeficiency
Absence fo fever
Clear nonpurulent discharge
Prior history of colic, food intolerance, ezema or other
allergic symptoms
A Positive family history of allergy
A Characteristic seasonal or exposure pattern
Poor respons to antibiotic
Good respons to antihistamines or bronchodilators
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Approach for Suspected Immune Deficiency are as
following:
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FAMILY HISTORY
Consanguinity of the parents
History of a sibling dying early in life of infections
Family history of an X-linked or autosomal recessive inheritance of a primary immunodeficiency
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GENERAL
• Complete blood count, including hemoglobin, differential white blood cell count(ALC , ANC) and morphology, and platelet count,ESR
• Radiographs to document infection in chest, sinus, mastoids, and long bones, if indicated by clinical history
• Cultures, if appropriate
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History Our Guide
• Predominant B-Cell defects– Onset after maternal antibodies diminish, usually
after 5-7 mos, later childhood to adulthood.– Bacteria: strep, staph, H.flu; Campylobacter,
enteroviruses, giardia, cryptosporidia– Recurrent sinopulmonary infections, chronic GI
symptoms, malabsorption, arthritis, viral meningoencephalitis
– Autoimmunity, lymphoreticular malignancy; thymoma, lymphoma
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SCREENING TESTS FOR B CELLIMMUNE FUNCTION
• Quantitative serum immunoglobulins• Specific antibodies to vaccine responses• Tetanus, diphtheria (IgG1)• Pneumococcal and meningococcal polysaccharides (IgG2)• Viral respiratory pathogens (IgG1 and IgG3)• Other vaccines: hepatitis B, influenza, MMR, polio (killed vaccine)• Isohemagglutinins (IgM antibodies to A and B blood group• antigens)• B cell quantitation by flow cytometry
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Laboratory Evaluation
• Qualitative Evaluation of Antibodies– Isohemagglutins – Antibodies to ABO blood-group
determinants– Antibodies to tetanus and diptheria glycoproteins
and pneumococcal polysaccharides.
• If low titers, give booster, then repeat titers 4 weeks later.
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History Our Guide
• Predominant T-Cell Defects– Early onset, usually 2-6 mos– Bacteria, mycobacteria, viruses: CMV, EBV,
varicella; fungi, parasites, PCP, -intracellulare– FTT, diarrhea, extensive mucocutaneous
candidiasis– GVHD caused by nonirradiated blood– Hypocalcemic tetany in infancy(DiGorje)
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SCREENING TESTS FOR T CELLIMMUNITY
• Newborn screening for TREC analysis (not available in iran)
• Absolute lymphocyte count• Chest radiograph for thymus shadow in
newborns• Delayed skin hypersensitivity to recall antigens• Quantification of T cell subsets
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History Our Guide for B and T cell defficiency
• ATAXIA TELLANGIECTASIA
• SCID
• WISKOTT- ALDERICHE SYNDROME
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History Our Guide
• Granulocyte Defects– Early onset, delayed separation of cord (>8 weeks),
poor wound healing(LAD)– Bacteria: staph, Pseudomonas, Serratia, Klebsiella;
Fungi: Candida, Nocardia, Aspergillus(CGD)– Dermatitis, impetigo, cellulitis, abscesses,
lymphadenitis, periodontitis, osteomyelits
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History Our Guide
• Complement Defects– Late (C5-C9) – Neisserial infections: meningitidis,
septic arthritis from gonorrhoeae.– Early (C1, C4, and C2) – autoimmune disease– C3 deficiency – overwhelming sepsis, especially
with gram negative organisms
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SCREENING TESTS FOR INNATEDEFENSE FACTORS
• Absolute granulocyte count, cell morphology• Serum total hemolytic complement for classic pathway
(CH50), alternative pathway hemolytic activity (AH50)• Nitroblue tetrazolium (NBT) test or flow cytometry
using dihydrorhodamine (DHR) « Staphylococcus aureus, Serratia marcescens, and Aspergillus”
• Flow cytometry for leukocyte adhesion molecules (CD11/CD18
• and CD15a)• IgE (JOB )
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B Cell Immunodeficiencies
• Bruton Bruton’ s (X-linked) Agammaglobulinemia• Autosomal Recessive Hyper-IgM Syndrome • X-linked Lymphoproliferative Syndrome• Transient Hypogammaglobulinemia of Infancy• Common Variable Immunodeficiency (CVID)• Selective IgA Deficiency • IgG Subclass Deficiency
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General Management of Patients withImmunodeficiency
• Avoid transfusions with blood products unless they are irradiated and cytomegalovirus-negative.
• Avoid live virus vaccines, especially in patients with severe T-cell deficiencies or agammaglobulinemia, and in household members.
• Use prophylaxis to Pneumocystis jiroveci (carinii) in T-cell immunodeficiency, and in X-linked hyper-IgM, consider antifungal prophylaxis in T-cell immunodeficiency.
• Follow pulmonary function in patients with recurrent pneumonia.
• Use chest physiotherapy and postural drainage in patients with recurrent pneumonia.
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• Consider using prophylactic antibiotics because minor infections can quickly disseminate.
• Examine diarrheal stools for Giardia lamblia and Clostridium difficile.
• Avoid unnecessary exposure to individuals with infection.
• Boil water for T-cell defects and hyper-IgM syndrome (Cryptosporidium risk).
• Use immunoglobulin for severe antibody deficiency states (400–600mg/kg q3–4 wk IV).
• BMT for T cell and Innate defect
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When IgG level are normal or near normal but Antibody deficiency is susceptible
IgG subclasses should be measured (IgG=70%, IgG 2 =20%, IgG3=7%, IgG4=3%)
Antibody function should be measured
In patient with selective IgA deficiency IgG subclasses should be measured
Many IgA deficiency patients have IgG2 subclass deficiency
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In older children and adults , a total Ig level above 800 mg/ dl with normal screening antibody test excludes antibody deficiency
Total Ig (IgG+IgM +IgA )< 400 or IgG level <200 mg /dl usually indicates antibody immunodeficiency
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