72 AUTOANTIBODIES

👩‍⚕️ Autoantibodies are one of the highest-yield topics in MRCS Part A. The exam loves antibody-to-disease pattern recognition: you are given a vignette with the classic triad, and you must pick the antibody — or vice versa. Master the master table below and you will pick up easy marks every paper.

How autoantibodies are used clinically

An autoantibody is an immunoglobulin directed against a self-antigen. They arise when central or peripheral tolerance breaks down. Three properties matter for the exam:

- Sensitivity — how often the antibody is positive in the disease (a good screen).

- Specificity — how rarely it appears outside that disease (a good confirmatory test).

- Activity correlation — whether the titre tracks disease activity (useful for monitoring).

A classic exam trap: confusing sensitive with specific. ANA is sensitive for SLE (positive in >95%) but very non-specific — it is positive in healthy elderly people, RA, Sjögren's and many other conditions. Anti-dsDNA and anti-Sm are specific for SLE, but only modestly sensitive. The same applies to RA: RF is sensitive but not specific; anti-CCP is specific.

👩‍⚕️ Rule of thumb — if a stem asks for the most specific antibody, you are usually looking past the screening test (ANA, RF) to the confirmatory one (anti-dsDNA/anti-Sm, anti-CCP).

The master autoantibody table

Autoantibody	Disease association	Exam-relevant pearls
ANA	SLE; also RA, Sjögren's, scleroderma, AIH	Highly sensitive for SLE (>95%) but non-specific; screening test
Anti-dsDNA	SLE	Specific; titre tracks activity, especially lupus nephritis
Anti-Sm	SLE	Highly specific but low sensitivity
Anti-histone	Drug-induced lupus	Think hydralazine, isoniazid, procainamide
Anti-Ro (SSA) / Anti-La (SSB)	Sjögren's; also SLE	Cross placenta → neonatal lupus and congenital heart block
Anti-Scl-70 (topoisomerase I)	Diffuse cutaneous systemic sclerosis	Widespread skin + early visceral involvement; worse prognosis
Anti-centromere	Limited cutaneous SS (CREST)	Calcinosis, Raynaud's, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
Anti-Jo-1 (anti-synthetase)	Polymyositis / dermatomyositis	Interstitial lung disease, mechanic's hands, Raynaud's
Rheumatoid factor (RF)	RA; also Sjögren's, endocarditis, hepatitis	Sensitive, not specific — IgM against Fc of IgG
Anti-CCP	Rheumatoid arthritis	Specific for RA; predicts erosive disease
c-ANCA (anti-PR3)	Granulomatosis with polyangiitis (Wegener's)	ENT + lung + kidney; saddle nose, haemoptysis, RPGN
p-ANCA (anti-MPO)	Microscopic polyangiitis; EGPA (Churg-Strauss); also UC, PSC, AIH	EGPA: asthma + eosinophilia + vasculitis
Anti-GBM	Goodpasture's syndrome	Pulmonary haemorrhage + crescentic GN; linear IgG on biopsy
Anti-mitochondrial (AMA)	Primary biliary cholangitis	Middle-aged woman, pruritus, raised ALP, raised IgM
Anti-smooth muscle (ASMA)	Autoimmune hepatitis type 1	Young woman, raised transaminases, raised IgG, responds to steroids
Anti-LKM-1	Autoimmune hepatitis type 2	Children/young women; more aggressive than type 1
Anti-TPO + anti-thyroglobulin	Hashimoto's thyroiditis; also seen in pernicious anaemia	Hypothyroid, lymphocytic infiltrate, Hürthle cells
TSI / TRAb (anti-TSH receptor)	Graves' disease	Stimulating antibody → hyperthyroidism, ophthalmopathy, pretibial myxoedema
Anti-intrinsic factor	Pernicious anaemia	Highly specific; blocks B12 absorption → megaloblastic anaemia
Anti-parietal cell	Pernicious anaemia	Sensitive, less specific; also atrophic gastritis
Anti-tTG (IgA) / anti-endomysial (EMA)	Coeliac disease	First-line: anti-tTG IgA (check total IgA to exclude deficiency)
Anti-GAD / anti-islet cell	Type 1 diabetes	Markers of autoimmune β-cell destruction
Anti-AChR	Myasthenia gravis	Fatigable weakness, ptosis, diplopia; thymoma association
Anti-MuSK	Myasthenia gravis (AChR-negative subset)	Bulbar predominant; poor response to AChE inhibitors
Anti-VGCC (voltage-gated calcium channel)	Lambert-Eaton myasthenic syndrome	Paraneoplastic — small cell lung cancer; strength improves with repetition
Anti-desmoglein 1 & 3	Pemphigus vulgaris	Intra-epidermal blisters, Nikolsky positive, mucosal involvement
Anti-hemidesmosome (BP180 / BP230)	Bullous pemphigoid	Sub-epidermal tense blisters, Nikolsky negative, elderly
Antiphospholipid (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I)	Antiphospholipid syndrome	Recurrent thrombosis, recurrent miscarriage, prolonged APTT that doesn't correct with mixing

Recommended

Image required:

A single-page infographic mapping antibody to disease, grouped by system (connective tissue, vasculitis, hepatobiliary, GI, endocrine, neuromuscular, dermatological, haematological).

Purpose:

Visual consolidation of the master table; serves as a quick-revision sheet the night before the exam.

Suggested source:

Custom infographic; alternatively adapt from Kumar & Clark or BMJ Best Practice.

High-yield clusters worth memorising

SLE — three tiers of antibodies

- ANA — screening (sensitive, not specific).

- Anti-dsDNA — specific; tracks activity and lupus nephritis.

- Anti-Sm — most specific but insensitive.

- Anti-Ro/La — pregnancy risk (neonatal lupus, congenital heart block).

- Anti-histone — think drug-induced lupus (hydralazine, isoniazid, procainamide).

Vasculitis — ANCA pattern

- c-ANCA / anti-PR3 ➡ GPA (Wegener's) — ENT, lung, kidney.

- p-ANCA / anti-MPO ➡ microscopic polyangiitis and EGPA (Churg-Strauss).

- Anti-GBM ➡ Goodpasture's — lung haemorrhage + crescentic GN.

- PAN is ANCA-negative and linked to hepatitis B — classic distractor.

Systemic sclerosis — limited vs diffuse

- Anti-centromere ➡ limited (CREST) — better prognosis; death from pulmonary hypertension.

- Anti-Scl-70 ➡ diffuse — early visceral involvement; death from renal crisis / pulmonary fibrosis.

Liver — three autoimmune diseases, three antibodies

- PBC ➡ AMA, raised ALP, pruritus, middle-aged woman.

- PSC ➡ p-ANCA, young man with UC, MRCP shows beading.

- Autoimmune hepatitis ➡ ASMA (type 1) or anti-LKM-1 (type 2), raised transaminases, raised IgG.

Bullous skin disease — depth defines the antibody

- Pemphigus vulgaris ➡ anti-desmoglein (intra-epidermal, Nikolsky positive, mucosa involved).

- Bullous pemphigoid ➡ anti-hemidesmosome BP180/230 (sub-epidermal, Nikolsky negative, mucosa spared).

👩‍⚕️ Memory hook: "Pemphigus is Painful and Positive Nikolsky; Bullous pemphigoid is Bigger, Benign-looking blisters and Nikolsky-negative." Pemphigus = desmosomes (cell-to-cell); pemphigoid = hemidesmosomes (cell-to-basement membrane).

Neuromuscular junction

- Myasthenia gravis ➡ anti-AChR (or anti-MuSK) — post-synaptic; weakness worsens with repetition; thymoma.

- Lambert-Eaton ➡ anti-VGCC — pre-synaptic; weakness improves with repetition; small cell lung cancer.

Antiphospholipid syndrome

- Triad of antibodies: lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I.

- Clinical: recurrent arterial and venous thrombosis, recurrent miscarriage, thrombocytopenia.

- Lab trap: prolonged APTT in vitro but prothrombotic in vivo; APTT does not correct with mixing study.

[Image: MCQs banner]

Test yourself

A 19-year-old man presents with mild jaundice, pale stools and known ulcerative colitis. Which antibody is most likely positive?

• ((Anti-phospholipid::APS causes thrombosis and miscarriage, not cholestasis.))
• ((Anti-endomysial::Coeliac disease — malabsorption, not obstructive jaundice.))
• ((Anti-mitochondrial (AMA)::PBC — middle-aged women, not young men with UC.))
• ((Anti-cardiolipin::Antiphospholipid syndrome — clotting, not cholestasis.))
• ((p-ANCA::☑️ PSC — young man with UC; MRCP shows beading of bile ducts.))

👩‍⚕️ UC + cholestasis in a young man = PSC until proven otherwise.

A woman presents with chronic pruritus and fatigue. ALP is raised and AMA is positive. What is the most likely diagnosis?

• ((Primary biliary cholangitis::☑️ AMA + raised ALP + pruritus + middle-aged woman is classical PBC.))
• ((Primary sclerosing cholangitis::p-ANCA, not AMA; young man with UC.))
• ((Autoimmune hepatitis::ASMA or anti-LKM; raised transaminases, not ALP.))
• ((Coeliac disease::Anti-tTG/EMA; malabsorption picture.))
• ((Drug-induced cholestasis::No autoantibody; needs drug history.))

Which antibody is most associated with pruritus and jaundice due to autoimmune bile duct destruction?

• ((AMA::☑️ Anti-mitochondrial antibody is the hallmark of PBC, positive in >95%.))
• ((p-ANCA::Associated with PSC, not PBC.))
• ((ANA::Non-specific; seen in many autoimmune conditions.))
• ((Anti-smooth muscle::Autoimmune hepatitis.))
• ((Anti-dsDNA::Specific for SLE.))

A 43-year-old woman is diagnosed with primary biliary cholangitis. What is the most specific antibody?

• ((AMA::☑️ Anti-mitochondrial antibody is highly specific for PBC; >95% of cases.))
• ((ANA::Present in PBC but non-specific.))
• ((Anti-smooth muscle::Points to autoimmune hepatitis.))
• ((p-ANCA::Associated with PSC.))
• ((Anti-dsDNA::Specific for SLE.))

👩‍⚕️ PBC management: ursodeoxycholic acid; advanced disease may require transplant.

A patient presents with symptoms of rheumatoid arthritis. Which is the most specific antibody?

• ((ANCA::Vasculitis, not RA.))
• ((ANA::Present in RA but very non-specific.))
• ((Anti-CCP::☑️ Most specific antibody for RA; predicts erosive disease.))
• ((AMA::PBC, not RA.))
• ((Rheumatoid factor::Sensitive but not specific — also positive in endocarditis, hepatitis, Sjögren's.))

👩‍⚕️ HLA-DR4 is the strongest genetic association in RA.

A woman presents with fatigue, dry eyes and dry mouth. What is the most likely diagnosis?

• ((Sjögren's syndrome::☑️ Sicca triad — fatigue, xerophthalmia, xerostomia; anti-Ro/anti-La positive.))
• ((SLE::Can cause fatigue but sicca symptoms point to Sjögren's.))
• ((Rheumatoid arthritis::Joints predominate, not sicca complex.))
• ((Sarcoidosis::Possible but rarer; look for bilateral hilar lymphadenopathy.))
• ((Hypothyroidism::Fatigue yes, but not sicca complex.))

A patient has positive anti-smooth muscle antibodies. What is the most likely diagnosis?

• ((Autoimmune hepatitis::☑️ ASMA is the hallmark; young women, raised transaminases, raised IgG, steroid-responsive.))
• ((PBC::Associated with AMA, not ASMA.))
• ((PSC::Associated with p-ANCA.))
• ((Hepatitis B::Viral serology, not autoantibody-mediated.))
• ((Wilson's disease::Low caeruloplasmin, raised urinary copper.))

c-ANCA is most associated with which condition?

• ((Granulomatosis with polyangiitis::☑️ Formerly Wegener's; c-ANCA targets PR3; ENT + lung + kidney.))
• ((Microscopic polyangiitis::p-ANCA (anti-MPO), not c-ANCA.))
• ((Eosinophilic granulomatosis with polyangiitis::Churg-Strauss — p-ANCA, asthma, eosinophilia.))
• ((Ulcerative colitis::p-ANCA.))
• ((Polyarteritis nodosa::ANCA-negative; linked to hepatitis B.))

p-ANCA is associated with which of the following?

• ((Granulomatosis with polyangiitis::c-ANCA, not p-ANCA.))
• ((Microscopic polyangiitis, UC and PSC::☑️ All three are p-ANCA (anti-MPO) associated.))
• ((SLE::Anti-dsDNA and ANA.))
• ((Rheumatoid arthritis::Anti-CCP and RF.))
• ((Polyarteritis nodosa::ANCA-negative; hepatitis B.))

Anti-dsDNA is most specific for which condition?

• ((SLE::☑️ Highly specific; titre tracks disease activity, especially lupus nephritis.))
• ((Sjögren's syndrome::Anti-Ro/anti-La.))
• ((Rheumatoid arthritis::Anti-CCP.))
• ((Drug-induced lupus::Anti-histone, not anti-dsDNA.))
• ((Mixed connective tissue disease::Anti-U1 RNP.))

👩‍⚕️ Rising anti-dsDNA + falling complement (C3/C4) = SLE flare, especially renal.

Anti-tissue transglutaminase (anti-tTG) is the first-line test for which condition?

• ((Coeliac disease::☑️ Anti-tTG IgA is first-line; confirm with duodenal biopsy showing villous atrophy.))
• ((Crohn's disease::Imaging and biopsy; no specific autoantibody.))
• ((Ulcerative colitis::p-ANCA, but not diagnostic.))
• ((Tropical sprue::Clinical diagnosis; no autoantibody.))
• ((Whipple's disease::PAS-positive macrophages on biopsy.))

👩‍⚕️ Always check total IgA — selective IgA deficiency is common in coeliac and gives false-negative anti-tTG.

Anti-centromere antibody is most associated with which condition?

• ((Limited cutaneous systemic sclerosis (CREST)::☑️ Calcinosis, Raynaud's, oEsophageal dysmotility, Sclerodactyly, Telangiectasia.))
• ((Diffuse cutaneous systemic sclerosis::Anti-Scl-70.))
• ((SLE::Anti-dsDNA.))
• ((Dermatomyositis::Anti-Jo-1.))
• ((Mixed connective tissue disease::Anti-U1 RNP.))

Anti-Scl-70 (anti-topoisomerase I) is most associated with which condition?

• ((Diffuse cutaneous systemic sclerosis::☑️ Widespread skin thickening, early visceral involvement, worse prognosis.))
• ((Limited cutaneous systemic sclerosis::Anti-centromere.))
• ((Polymyositis::Anti-Jo-1.))
• ((SLE::Anti-dsDNA.))
• ((Rheumatoid arthritis::Anti-CCP.))

Anti-Jo-1 antibody is most associated with which condition?

• ((Polymyositis/dermatomyositis::☑️ Anti-synthetase syndrome — ILD, mechanic's hands, Raynaud's.))
• ((Inclusion body myositis::No specific autoantibody; diagnosed on biopsy.))
• ((Myasthenia gravis::Anti-AChR or anti-MuSK.))
• ((SLE::Anti-dsDNA.))
• ((Diffuse systemic sclerosis::Anti-Scl-70.))

A patient has Raynaud's, sclerodactyly, oesophageal dysmotility and telangiectasia. Which antibody is most likely positive?

• ((Anti-centromere::☑️ CREST = limited cutaneous systemic sclerosis; anti-centromere is the marker.))
• ((Anti-Scl-70::Diffuse, not limited, scleroderma.))
• ((ANA::Often positive but non-specific.))
• ((Anti-dsDNA::Specific for SLE.))
• ((Anti-Ro::Sjögren's syndrome.))

👩‍⚕️ Pulmonary hypertension is the leading cause of death in CREST; renal crisis dominates in diffuse disease.

A 35-year-old woman has three unexplained miscarriages and a prolonged APTT that doesn't correct on mixing. Which antibody is most likely positive?

• ((Lupus anticoagulant::☑️ Antiphospholipid syndrome — recurrent miscarriage, thrombosis, paradoxical APTT prolongation.))
• ((Anti-dsDNA::SLE marker; APS can coexist but doesn't cause the APTT pattern.))
• ((Anti-Ro::Neonatal lupus and congenital heart block, not recurrent miscarriage with this lab pattern.))
• ((Anti-CCP::Rheumatoid arthritis.))
• ((Anti-tTG::Coeliac disease.))

A 45-year-old smoker has proximal weakness that improves with repeated effort. Which antibody is most likely positive?

• ((Anti-AChR::Myasthenia gravis — weakness worsens with repetition.))
• ((Anti-MuSK::Myasthenia gravis subtype, bulbar predominant.))
• ((Anti-VGCC::☑️ Lambert-Eaton — paraneoplastic, small cell lung cancer; strength improves with repetition.))
• ((Anti-GAD::Type 1 diabetes; also stiff-person syndrome.))
• ((Anti-Jo-1::Polymyositis — proximal weakness but no facilitation phenomenon.))

An elderly man develops tense sub-epidermal blisters with a negative Nikolsky sign. Which antibody is most likely positive?

• ((Anti-desmoglein 3::Pemphigus vulgaris — intra-epidermal blisters, positive Nikolsky.))
• ((Anti-BP180 / BP230::☑️ Bullous pemphigoid — sub-epidermal, tense blisters, Nikolsky negative, elderly.))
• ((Anti-tTG::Dermatitis herpetiformis is the coeliac skin manifestation, but blisters are small and itchy.))
• ((Anti-Ro::Subacute cutaneous lupus, not bullous disease.))
• ((Anti-Scl-70::Skin thickening in scleroderma, not blisters.))

A 28-year-old woman has fatigue, polyuria and weight loss; fasting glucose is 18 mmol/L. Which antibody pair is most diagnostic?

• ((Anti-GAD and anti-islet cell::☑️ Type 1 diabetes — autoimmune β-cell destruction.))
• ((Anti-TPO and anti-Tg::Hashimoto's thyroiditis; may coexist but not diagnostic of T1DM.))
• ((Anti-IF and anti-parietal cell::Pernicious anaemia.))
• ((Anti-AChR and anti-MuSK::Myasthenia gravis.))
• ((TSI / TRAb::Graves' disease.))

Revision summary

- ANA — sensitive screen for SLE; non-specific.

- Anti-dsDNA / anti-Sm — specific for SLE; dsDNA tracks lupus nephritis.

- Anti-Ro/La — Sjögren's; neonatal lupus + congenital heart block.

- Anti-histone — drug-induced lupus.

- Anti-Scl-70 — diffuse scleroderma. Anti-centromere — limited (CREST).

- Anti-Jo-1 — polymyositis/dermatomyositis with ILD.

- RF — sensitive for RA. Anti-CCP — specific for RA.

- c-ANCA / PR3 — GPA (Wegener's). p-ANCA / MPO — MPA, EGPA, UC, PSC.

- Anti-GBM — Goodpasture's (lung + kidney).

- AMA — PBC. ASMA — AIH type 1. Anti-LKM — AIH type 2. p-ANCA — PSC.

- Anti-TPO / anti-Tg — Hashimoto's. TSI / TRAb — Graves'.

- Anti-IF + anti-parietal cell — pernicious anaemia.

- Anti-tTG / anti-EMA — coeliac (check IgA).

- Anti-GAD / anti-islet — T1DM.

- Anti-AChR / MuSK — myasthenia gravis (worsens with repetition; thymoma).

- Anti-VGCC — Lambert-Eaton (improves with repetition; small cell lung cancer).

- Anti-desmoglein — pemphigus (intra-epidermal, Nikolsky +).

- Anti-BP180/230 — bullous pemphigoid (sub-epidermal, Nikolsky −).

- Antiphospholipid (LA, ACL, anti-β2-GPI) — APS: thrombosis, miscarriage, paradoxical APTT.