STEPTRACKERIMMUNOLOGY + RHEUMATOLOGY | AUTOIMMUNITY | HIGH-YIELD REVIEW

Autoantibodies

One table to match each autoantibody to its disease — and to know which are sensitive screening tests and which are specific enough to confirm.

FOCUS ON

ANA: sensitive for SLE (> 95%), not specific. Anti-dsDNA and anti-Smith: specific for SLE (dsDNA tracks nephritis activity). Anti-histone: drug-induced lupus. Anti-Ro/SSA, anti-La/SSB: Sjögren, neonatal lupus (congenital heart block). Anti-U1 RNP: mixed connective tissue disease. Anti-Scl-70 (topoisomerase I): diffuse scleroderma; anti-centromere: limited (CREST). Anti-Jo-1, anti-Mi-2, anti-SRP: myositis. RF and anti-CCP (more specific): RA. c-ANCA (PR3): granulomatosis with polyangiitis; p-ANCA (MPO): microscopic polyangiitis, EGPA. Antiphospholipid (lupus anticoagulant, anticardiolipin, anti-β2GPI): thrombosis, miscarriage, false ⁺ VDRL, prolonged PTT. Organ-specific: anti-TPO, TSI, anti-GAD, anti-tTG, anti-AChR, anti-mitochondrial, anti-smooth muscle.

AUTOANTIBODY

DISEASE

NOTE

SENSITIVE · SPECIFIC

Antinuclear (ANA)

SLE; also Sjögren, scleroderma, drug lupus, healthy elderly

Screening test

Sensitive

Anti-dsDNA · anti-Smith

SLE

dsDNA correlates with lupus nephritis and flares

Specific

Anti-histone

Drug-induced lupus

Procainamide, hydralazine, isoniazid

—

Anti-Ro/SSA · anti-La/SSB

Sjögren, SLE (subacute cutaneous)

Cross placenta → neonatal lupus, complete heart block

Screen pregnant women with SLE/Sjögren

Anti-U1 RNP

Mixed connective tissue disease

Raynaud, swollen hands, myositis, lupus and scleroderma features

Very high titer

Anti-Scl-70 (topoisomerase I)

Diffuse systemic sclerosis

Interstitial lung disease risk

Specific

Anti-centromere

Limited scleroderma (CREST)

Pulmonary hypertension risk

—

Anti-RNA polymerase III

Diffuse scleroderma

Scleroderma renal crisis

—

Anti-Jo-1 · anti-Mi-2 · anti-SRP

Polymyositis/dermatomyositis

Jo-1: interstitial lung disease, mechanic's hands · Mi-2: dermatomyositis · SRP: necrotizing

Anti-TIF1γ → cancer-associated DM

Rheumatoid factor · anti-CCP

Rheumatoid arthritis

RF = IgM against IgG Fc (also in Sjögren, HCV, endocarditis)

Anti-CCP more specific

PR3-ANCA (c-ANCA)

Granulomatosis with polyangiitis

Sinus, lung, kidney

—

MPO-ANCA (p-ANCA)

Microscopic polyangiitis, EGPA, pauci-immune GN

Also UC, primary sclerosing cholangitis

—

Antiphospholipid antibodies

Antiphospholipid syndrome (primary or with SLE)

Arterial/venous thrombosis, recurrent miscarriage, livedo; paradoxically prolonged PTT; false ⁺ VDRL

Repeat at 12 weeks · warfarin

Organ-specific antibodies

Anti-TPO (Hashimoto) · TSI (Graves) · anti-GAD, anti-IA2 (type 1 DM) · anti-tTG, anti-endomysial IgA (celiac) · anti-AChR (myasthenia) · anti-VGCC (Lambert-Eaton) · anti-mitochondrial (PBC) · anti-smooth muscle, anti-LKM1 (autoimmune hepatitis) · anti-parietal cell, anti-IF (pernicious anemia) · anti-PLA2R (membranous) · anti-desmoglein (pemphigus) · anti-BP180 (pemphigoid) · anti-GBM (Goodpasture) · anti-aquaporin-4 (NMO) · anti-NMDA receptor (encephalitis)

Match to organ

Check total IgA when testing celiac

Mechanism — why antiphospholipid prolongs PTT yet clots

Antibody binds phospholipid–β2GPI

→

In the test tubeBlocks phospholipid → PTT ↑

In the bodyActivates endothelium, platelets, complement

→

Thrombosis, placental infarcts

Screen vs confirm

DISEASE

SENSITIVE SCREEN

SPECIFIC CONFIRM

SLE

ANA

Anti-dsDNA, anti-Smith

Anti-CCP

Celiac

IgA anti-tTG

Biopsy, anti-endomysial

Scleroderma

ANA

Anti-Scl-70, anti-centromere

How it's tested

COMMON CONFUSIONc-ANCA/PR3 (granulomatosis with polyangiitis: sinus, lung, kidney) vs p-ANCA/MPO (microscopic polyangiitis without granulomas; EGPA with asthma and eosinophils).

THE TRAPA negative ANA nearly rules out SLE, but a positive ANA alone doesn't make the diagnosis.

YOUR APPROACHClinical pattern → screening antibody → specific confirmatory antibody → organ risk tied to that antibody.

If you see… think…

Best screening test for SLE → ANA

Antibody tracking lupus nephritis → anti-dsDNA

Newborn with complete heart block, mother with Sjögren → anti-Ro/SSA

Raynaud, puffy hands, very high anti-U1 RNP → MCTD

Calcinosis, Raynaud, telangiectasia, anti-centromere → limited scleroderma

Myositis + ILD + mechanic's hands → anti-Jo-1

Most specific RA antibody → anti-CCP

Saddle nose, hemoptysis, hematuria, PR3-ANCA → granulomatosis with polyangiitis

Recurrent miscarriages with prolonged PTT → antiphospholipid syndrome

Pruritus, ↑ ALP, anti-mitochondrial antibody in a woman → primary biliary cholangitis