1. DIAGNOSIS of AUTOIMMUNE DISEASES Assos. Prof. Gülderen Yanıkkaya Demirel MD, PhD Yeditepe University School of Medicine Immunology Department, Medical Microbiology Department Yeditepe University Hospital, Hematology Department Director of Stem Cell Laboratory gulderen.ydemirel@yeditepe.edu.tr

2. 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

3. AUTOIMMUNITY TAUTOLOGY

4. GEOGRAPHICAL DISTRIBUTION AND PREVALANCE of AUTOIMMUNE DISEASES DiseasePrevalance 1/100,000 Region Systemic lupus erytematosus 34 – 150 42 45 USA, Spain, Greece Canada Austria Multiple sclerosis 177 – 358 101 46 USA, Canada Turkey Norway Sjögren Syndrome 600 110 3500 Greece Denmark United Kingdom

5. GEOGRAPHICAL DISTRIBUTION of T1D

6. GEOGRAPHICAL DISTRIBUTION of MS

7. GEOGRAPHICAL DISTRIBUTION of UC

8. X CHROMOSOME and SEX RATIO of AUTOIMMUNITY

9. INFECTIONS SEEN IN AUTOIMMUNE DISEASES DiseaseInfection Agents Romatoid arthritisEpstein-Barr virus (EBV) Parvo B19 Chronic Hepatitis C virus (KHCV) Multiple sclerosisEBV Chlamidopiliya Type-1 DiabetesCoxsachie virus B (Cox B) Cytomegalovirus Mumps Sjögren SyndromeCox B EBV CHCV

10. SPECIFIC AUTOANTIBODIES – ANTIGENIC DETERMINANT and CLINICAL REFLECTIONS Anti-dsDNA dsDNA High specificity for SLE; often correlates with active severe disease Anti–extractable nuclear antigensSmithHigh specificity for SLE Anti-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

11. IT IS NOT ALWAYS EASY TO DIAGNOSE AN AUTOIMMUNE DISEASE

12. TOOLS for DIAGNOSIS HISTORY PHYSICAL EXAMINATION LABORATORY DIAGNOSIS IMAGING TECHNIQUES

13. 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

14. TESTS TO BE REQUESTED AT FIRST VISIT Blood count CRP ANA (if one is strongly suspicious about AID)

15. ANA – ANTI NUCLEAR ANTIBODY The antibodies that target “normal” proteins within the nucleus of a cell are called antinuclear antibodies (ANA).

16. 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.

17. 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.

19. EXAMPLES of DISEASE-TEST RELATION

20. METHODS for AUTOANTIB0DY MEASUREMENT

21. 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

22. ANA ALGORITHM