Download AUTOANTIBODIES IN RHEUMATOLOGY

AUTOANTIBODIES IN
RHEUMATOLOGY
G. Cooke
VTS Trainee
AIMS & OBJECTIVES


Nothing radical
Just to enhance consideration of the
role of autoantibody titres when…
Considering rheumatological diagnosis
 Assessing for exacerbation / treatment
response
 Interpreting results / letters

Introduction (1):
Autoantibodies??
- Immunoglobulins
- Detectable in people with a variety of
clinical presentations & in healthy
individuals
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?
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
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 (1030% RA patients seronegative)
RHEUMATOID FACTOR (3):
- High titres  severe articular / extraarticular disease in RA
- Levels don’t alter significantly with Rx
- 80% sensitivity (therefore –ve doesn’t
exclude diagnosis)
- PPV 50%
RHEUMATOID FACTOR (4):
- RF +ve patients? Also consider…
-
SLE / Sjogrens
SBE
Dermatomyositis
EBV
Cirrhosis
Renal disease
-
Chronic viruses
TB
Scleroderma
Leukaemia
Syphilis
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)
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)
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
Nucleolar: Scleroderma / Polymyositis
ANTI-NUCLEAR ANTIBODIES (4):
Diagnosis
% ANA +ve
Specific ABs
RA
15-35%
RF
SLE
>95%
Systemic Sclerosis
60-90%
Mixed CTD
95-99%
Anti-Sm / Anti
ds-DNA
Anti-centromere /
Anti-Scl-70
Anti-RNP
Polymyositis /
Dermatomyositis
25%
Anti-Jo
Sjogren’s Syndrome
75%
Anti-Ro / Anti-La
ANTI-NUCLEAR ANTIBODIES (5):
- +ve ANA also a/w…
- Chronic Hepatitis
- EBV
- Myaesthenia Gravis
- PAN
- Leukaemia
- Cirrhosis
- Order an ANA when…
- Support diagnosis of CTD when suspected
clinically (FU with specific tests)
- To exclude SLE with 1-2 features and no clear
alternative
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)
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
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
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 CTD
RA
SLE
Sjogren’s
Polymyositis
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
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
CONCLUSION:
- Think before you request
- Clinical impression hugely valuable in
guiding Ix choice
- Sensitive tests first… specific later to
confirm diagnoses