1. AUTOANTIBODIES IN RHEUMATOLOGY G. Cooke VTS Trainee

2. AIMS & OBJECTIVES Nothing radical Nothing radical Just to enhance consideration of the role of autoantibody titres when… Just to enhance consideration of the role of autoantibody titres when… Considering rheumatological diagnosis Considering rheumatological diagnosis Assessing for exacerbation / treatment response Assessing for exacerbation / treatment response Interpreting results / letters Interpreting results / letters

3. Introduction (1): Autoantibodies?? -Immunoglobulins - Detectable in people with a variety of clinical presentations & in healthy individuals

4. Introduction (2): - No autoantibody confirms a diagnosis or determines treatment – adjunctive role predominantly - Ask – Will knowing the value of x, y or z alter my management of this patient?

5. RHEUMATOID FACTOR (1): - IgM which reacts with the fc component of abnormal, antigenic IgG to produce immune complexes  complement activation…inflammatory cascade - Present in 1% of healthy individuals - Present in 70-90% of RA patients - Levels increase with age

6. RHEUMATOID FACTOR (2): - Blood titres >1:80 considered +ve and suggestive of RA - Titres between “unidentifiable” and 1:80 – consider: SLE, Sjogrens (or healthy) - “unidentifiable” titres don’t exclude RA (10- 30% RA patients seronegative)

7. RHEUMATOID FACTOR (3): - High titres  severe articular / extra- articular disease in RA - Levels don’t alter significantly with Rx - 80% sensitivity (therefore –ve doesn’t exclude diagnosis) - PPV 50%

8. RHEUMATOID FACTOR (4): - RF +ve patients? Also consider… - SLE / Sjogrens- Chronic viruses - SBE- TB - Dermatomyositis- Scleroderma - EBV- Leukaemia - Cirrhosis- Syphilis - Renal disease

9. ANTI-NUCLEAR ANTIBODIES (1): - Strongly associated with SLE (but also other rheumatological conditions, bizarre syndromes and healthy people) - MULTIPLE subtypes of Anti-Nuclear Antibodies (ANA, ds-DNA, ss-DNA, anti-DNP, SS-A, SS-B, Scl-70, RNP, RANA, RAP, Antimicrosomal, Antithyroglobulin, ASMA)

10. ANTI-NUCLEAR ANTIBODIES (2): - 95% SLE have +ve ANA (good sens – -ve test good for exclusion of SLE) - Specificity for ANA in SLE low (57% - +ve ANA not great at confirming SLE) [false +ve with MULTIPLE medications] - If lupus personified walks in – check ANA, if a bit grey, probably not worth it - Doesn’t reflect disease activityin SLE (use clinical features / ESR / C3 / C4 / dsDNA)

11. ANTI-NUCLEAR ANTIBODIES (3): - More confusion… Different patterns when studies under UV microscopy and ANA subgrouped accordingly (often referred to in clinic letters / ICE results): Homogenous: SLE / Mixed CTD Peripheral: SLE Speckled: SLE / Sjogrens / Scleroderma Polymyositis / RA / Mixed CTD Polymyositis / RA / Mixed CTD Nucleolar: Scleroderma / Polymyositis

12. ANTI-NUCLEAR ANTIBODIES (4): Diagnosis % ANA +ve Specific ABs RA15-35%RF SLE>95% Anti-Sm / Anti ds-DNA Systemic Sclerosis 60-90% Anti-centromere / Anti-Scl-70 Mixed CTD 95-99%Anti-RNP Polymyositis / Dermatomyositis 25%Anti-Jo Sjogren’s Syndrome 75% Anti-Ro / Anti-La

13. ANTI-NUCLEAR ANTIBODIES (5): - +ve ANA also a/w… - Chronic Hepatitis- PAN - EBV- Leukaemia - Myaesthenia Gravis- Cirrhosis - Order an ANA when… - Support diagnosis of CTD when suspected clinically (FU with specific tests) clinically (FU with specific tests) - To exclude SLE with 1-2 features and no clear alternative alternative

14. ANTI-ds-DNA ANTIBODIES: - Less sensitive but more specific for SLE compared to ANA - Very low false +ve rate - Do relate to disease activity – esp. renal involvement (e.g. monitoring lupus nephritis)

15. ANTI-Sm ANTIBODIES: - AKA Anti-Smith (not smooth muscle) - V. SLE specific – but present in 30% cases so not particularly sensitive for SLE - Associated with severity and extent of renal involvement - False +ve a/w EBV – molecular mimicry

16. ANTI-RNP (ribonuclear protein) ANTIBODIES: - Poor sensitivity and specificity for SLE - Present in 40% SLE patients - High levels diagnostic of Mixed CTD - A/W milder renal disease & Raynaud’s

17. ANTI-SCLERODERMA ANTIBODIES: - Scl-70 / Scleroderma Abs - Present in 45% with scleroderma (PSS) - Scl-70 titre relates to both likelihood of diagnosis, and disease activity - Absence doesn’t exclude scleroderma - Also a/w: Mixed CTDSLESjogren’s RAPolymyositis

18. Anti-Ro / Anti-La / Anti-SS-C (1): - Confusingly, Anti-Ro = Anti-SS-A Anti La = Anti-SS-B - SS-A / SS-B – used to diagnose Sjogren’s (Prim / Sec) - SS-A in 60-70% Primary Sjogren’s; SS-B in 50% (SS-A + SS- B +ve = confirms diagnosis) - Can differentiate between 1° & 2° Sjogren’s – SS-B found only in 1° disease

19. Anti-Ro / Anti-La / Anti-SS-C (2): - SS-A found in 25% SLE cases (present in the majority of ANA-ve SLE patients) / SS-B never found in SLE - SS-C +ve in 75% RA patients / RA + 2° Sjogren’s - High Anti-SS levels…  Sjogren’s more likely  Disease more active - Anti-SS levels fall with treatent

20. CONCLUSION: - Think before you request - Clinical impression hugely valuable in guiding Ix choice - Sensitive tests first… specific later to confirm diagnoses