DIAGNOSIS of AUTOIMMUNE DISEASES

Assos. Prof. Gülderen Yanıkkaya Demirel MD, PhDYeditepe University School of Medicine

Immunology Department, Medical Microbiology Department

Yeditepe University Hospital, Hematology DepartmentDirector of Stem Cell Laboratory

gulderen.ydemirel@yeditepe.edu.tr

DEFINITION of AUTOIMMUNITY

Sometimes antibodies make a mistake, identifying normal, naturally-

occurring proteins in our bodies as being "foreign" and dangerous.

http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ana.asp

AUTOIMMUNITY TAUTOLOGY

GEOGRAPHICAL DISTRIBUTION AND PREVALANCE of AUTOIMMUNE DISEASES

Disease Prevalance1/100,000

Region

Systemic lupus erytematosus 34 – 150

4245

USA, Spain, GreeceCanadaAustria

Multiple sclerosis177 – 358

10146

USA, CanadaTurkeyNorway

Sjögren Syndrome600110

3500

GreeceDenmarkUnited Kingdom

GEOGRAPHICAL DISTRIBUTION of T1D

GEOGRAPHICAL DISTRIBUTION of MS

GEOGRAPHICAL DISTRIBUTION of UC

INFECTIONS SEEN IN AUTOIMMUNE DISEASES

Disease Infection Agents

Romatoid arthritis Epstein-Barr virus (EBV)Parvo B19Chronic Hepatitis C virus (KHCV)

Multiple sclerosis EBVChlamidopiliya

Type-1 Diabetes Coxsachie virus B (Cox B)CytomegalovirusMumps

Sjögren Syndrome Cox BEBVCHCV

SPECIFIC AUTOANTIBODIES – ANTIGENIC DETERMINANT and

CLINICAL REFLECTIONSAnti-dsDNA dsDNA High specificity for SLE; often correlates

with active severe disease

Anti–extractable nuclear antigens Smith High specificity for SLEAnti-Sm Proteins containing U1-RNA

Anti-RNP MCTD, SLE, RA, scleroderma, Sjögren

syndrome

Anti-SSA (Ro) RNPs Sjögren syndrome, SLE (subacute cutaneous lupus),neonatal lupus,

Anti-SSB (La) RNPs Sjögren syndrome, SLE, neonatal SLE

Anticentromere Centromere/kinetochore region Limited scleroderma, pulmonary of chromosome hypertension, primar biliary cirrhosis

Anti–Scl 70 DNA topoisomerase I Diffuse scleroderma

Anti–Jo-1 (anti-synthetase antibodies) Histidyl tRNA synthetase Inflammatory myopathies with (other tRNA synthetases) interstitial lung disease, fever and

arthritis Anti-SRP Antibody to signal recognition protein Inflammatory myopathies with poor

prognosis

Anti-PM/Scl Antibody to nucleolar granular PM/scleroderma overlap syndrome component

Anti–Mi-2 Antibodies to a nucleolar antigen DM of unknown function

IT IS NOT ALWAYS EASY

TO DIAGNOSE

AN AUTOIMMUNE DISEASE

TOOLS for DIAGNOSIS

HISTORY

PHYSICAL EXAMINATION

LABORATORY DIAGNOSIS

IMAGING TECHNIQUES

LABORATORY DIAGNOSIS• INFLAMMATION MARKERS AND BODY FLUID TESTING

– Blood count – ESR – Erythrocyte Sedimentation Rate– CRP – C-Reactive Protein– Ferritin– Oligoclonal band– Immunophenotyping

• AUTOANTIBODY TESTS– ANA – Anti nuclear antibody– dsDNA – doble stranded DNA– ENA – Anti-extractable nuclear antigen– RF – Rheumatoid Factor– Anti-CCP – Autoantibodies to cyclic citrullinated peptide– Complement– Immunoglobulins– Cryoglobulins

TESTS TO BE REQUESTED AT FIRST VISIT

• Blood count• CRP• ANA (if one is strongly suspicious about AID)

ANA – ANTI NUCLEAR ANTIBODY

The antibodies that target “normal” proteins within the nucleus of a cell

are called antinuclear antibodies (ANA).

WHAT IS AN ANTIBODY or ANA?

Antibodies develop in our immune system to help the body fight infectious organisms.

When an antibody recognizes the foreign proteins of an infectious organism, it recruits other proteins and cells to fight off the infection. This cascade of attack is called inflammation.

Unfortunately, some antibodies make incorrect calls, identifying a naturally-occurring protein (or self protein) as foreign. These autoantibodies start the cascade of inflammation, causing the body to attack itself.

Most of us have autoantibodies, but typically in small amounts. The presence of large amount of autoantibodies or ANAs can indicate an autoimmune disease.

FAST FACTS

A positive ANA test means autoantibodies are present.

By itself, a positive ANA test does not indicate the presence of an autoimmune disease or the need for therapy.

Autoimmune diseases can be treated.

EXAMPLES of DISEASE-TEST RELATION

METHODS for AUTOANTIB0DY MEASUREMENT

What does a positive ANA reading mean?

A negative ANA reading means no autoantibodies are present in the body. However, a positive ANA reading alone does not indicate an autoimmune disease. Why?

The prevalence of ANAs in healthy individuals is about 3-15%. The production of these autoantibodies is strongly age-dependent, and increases to 10-37% in healthy persons over the age of 65. Even healthy people with viral infections can have a positive ANA, albeit for a short time.

Some medications can cause a positive ANA. It is important to talk with your doctor all the drugs you are taking—prescription, over-the-counter and street. Other conditions, such as cancer, can cause a positive ANA.

The positive ANA reading simply tells your doctor to keep looking. In fact, you may have a “false positive” ANA, which means that the evidence is not there to make a diagnosis of lupus or any other autoimmune disease. To make a definite diagnosis, your doctor will need more blood tests along with history of your symptoms and a physical examination. http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ana.asp

ANA ALGORITHM