SN12 SHORT NOTE 5M

Write a short note on autoantibodies in rheumatology, including antinuclear antibodies.

General Medicine · Final Professional

Introduction

Autoantibodies are central to the diagnosis, classification and prognosis of connective tissue disease, but they must always be interpreted in the context of the clinical picture. Ordering them indiscriminately generates false positives, unnecessary anxiety and inappropriate referral — they are confirmatory tests, not screening tests for undifferentiated symptoms.

Antinuclear Antibody (ana)

Detected by indirect immunofluorescence on HEp-2 cells, the reference method, reported as a titre and a pattern.
Highly sensitive but poorly specific. ANA is positive in up to 15% of healthy people at low titre (and more with increasing age), in relatives of patients with autoimmune disease, in chronic infection, in thyroid and liver autoimmunity, and in malignancy.
Titre matters: 1:40 to 1:80 is often insignificant; 1:160 and above is more likely to be meaningful in the right clinical setting.
A negative ANA makes SLE very unlikely (sensitivity > 95%) — this is its greatest value.

ANA Pattern	Typical Target	Association
Homogeneous	dsDNA, histones	SLE, drug-induced lupus
Speckled	Sm, RNP, Ro, La	SLE, MCTD, Sjögren's, systemic sclerosis
Nucleolar	RNA polymerase, fibrillarin	Systemic sclerosis (diffuse)
Centromere	Centromere proteins	Limited cutaneous systemic sclerosis (CREST)
Cytoplasmic	Jo-1, ribosomal P	Antisynthetase syndrome, myositis, SLE

Specific Autoantibodies

Antibody	Principal Disease	Comment
Anti-dsDNA	SLE	Specific; titres track activity, especially nephritis
Anti-Sm	SLE	Most specific for SLE; sensitivity only 20–30%
Anti-histone	Drug-induced lupus	Also in idiopathic SLE
Anti-Ro (SSA) / Anti-La (SSB)	Sjögren's syndrome, SCLE, neonatal lupus with congenital heart block	Ro can be positive in ANA-negative lupus
Anti-U1-RNP	Mixed connective tissue disease	Required in high titre for MCTD
Anti-centromere	Limited systemic sclerosis	Associated with pulmonary hypertension
Anti-Scl-70 (topoisomerase I)	Diffuse systemic sclerosis	Associated with interstitial lung disease
Anti-RNA polymerase III	Diffuse systemic sclerosis	Scleroderma renal crisis; malignancy association
Anti-Jo-1	Antisynthetase syndrome	Myositis with ILD, mechanic's hands, Raynaud's
Anti-TIF1-gamma, anti-NXP2	Dermatomyositis	Malignancy-associated
Anti-MDA5	Amyopathic dermatomyositis	Rapidly progressive ILD

Non-ana Autoantibodies

Rheumatoid factor — IgM anti-IgG Fc. Positive in ~70% of RA, but also in Sjögren's syndrome (high titre), SLE, chronic infection (infective endocarditis, tuberculosis, hepatitis C, leprosy), and 5–10% of healthy elderly. Not diagnostic on its own.
Anti-CCP — ~95% specific for RA; predicts erosive disease; may precede symptoms by years.
ANCA — c-ANCA/anti-PR3 with granulomatosis with polyangiitis; p-ANCA/anti-MPO with microscopic polyangiitis and EGPA. Also positive in infection and drug-induced vasculitis.
Antiphospholipid antibodies — lupus anticoagulant, anticardiolipin, anti-beta-2 glycoprotein I; must be confirmed 12 weeks apart.
Anti-GBM — Goodpasture's disease (pulmonary-renal syndrome).
Complement C3 and C4 — low in active SLE and in cryoglobulinaemia, reflecting consumption; useful for monitoring rather than diagnosis.

EXAM TIP

The two lines examiners most want to hear are: "ANA is a sensitive screening test but not specific — anti-dsDNA and anti-Sm are the specific ones", and "autoantibodies must be interpreted alongside the clinical features; a positive ANA alone does not diagnose lupus." Ordering an "autoimmune panel" in a patient with isolated arthralgia and no other features is poor practice, and knowing that is worth marks.

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