SN2 SHORT NOTE 5M ★ High-yield

Describe the important autoantibodies with their disease associations.

Pathology · 2nd Professional — Para-Clinical

Autoantibodies are antibodies directed against the individual’s own antigens, arising from a breakdown of immunological self-tolerance.

Their presence does not always mean disease — low-titre autoantibodies occur in healthy people, especially the elderly
They may be pathogenic, or merely a marker, and distinguishing the two matters clinically

Antibody	Disease
Anti-thyroid peroxidase, anti-thyroglobulin	Hashimoto thyroiditis
Anti-TSH receptor (stimulating)	Graves disease
Anti-acetylcholine receptor	Myasthenia gravis
Anti-intrinsic factor, anti-parietal cell	Pernicious anaemia
Anti-glomerular basement membrane	Goodpasture syndrome
Anti-desmoglein	Pemphigus vulgaris
Anti-mitochondrial	Primary biliary cholangitis — over 95%
Anti-endomysial, anti-tissue transglutaminase	Coeliac disease

Antibody	Disease	Note
ANA	SLE and most connective tissue disease	Sensitive, not specific — a screening test
Anti-dsDNA	SLE	Specific; tracks disease activity and nephritis
Anti-Sm	SLE	The most specific for lupus
Anti-histone	Drug-induced lupus	—
Anti-Ro/La	Sjogren syndrome; neonatal lupus	Cross the placenta — congenital heart block
Anti-centromere	Limited systemic sclerosis (crest)	Better prognosis
Anti-Scl-70 (topoisomerase I)	Diffuse systemic sclerosis	Associated with pulmonary fibrosis
Rheumatoid factor	Rheumatoid arthritis	An IgM antibody against the Fc of IgG; also positive in infection and in the elderly
Anti-CCP	Rheumatoid arthritis	Far more specific than rheumatoid factor; predicts erosive disease
C-ANCA (anti-proteinase 3)	Granulomatosis with polyangiitis	—
P-ANCA (anti-myeloperoxidase)	Microscopic polyangiitis	—

CLINICAL PEARL

Sensitivity and specificity are used for opposite purposes, and the pairs above illustrate it.
ANA and rheumatoid factor are sensitive, so a negative result is useful for excluding disease.
Anti-Sm and anti-CCP are specific, so a positive result is useful for confirming it. Ordering the wrong one for the question being asked is among the commonest errors in practice.

Failure of central or peripheral tolerance — autoreactive clones are not deleted or suppressed
Molecular mimicry — a microbial antigen resembles a self antigen; the basis of rheumatic fever after streptococcal infection
Genetic susceptibility — particularly HLA type

Test for a specific question, not as a screen — an unselected autoantibody panel produces false positives and enormous confusion
Titre matters — a low-titre ANA of 1:40 is often meaningless, whereas 1:640 with a homogeneous pattern is significant
Anti-Ro crosses the placenta, so a pregnant woman with these antibodies needs fetal cardiac monitoring for heart block
Treatment is directed at the disease, not the antibody — falling titres are reassuring but are not by themselves an indication to change treatment

All questions in Immunopathology