SN6 SHORT NOTE 5M ★ High-yield

Define autoimmunity. Describe its mechanisms, classification and the autoantibodies of diagnostic value.

Microbiology · 2nd Professional — Para-Clinical

Definition and Mechanisms

Autoimmunity is an immune response directed against the host’s own tissues, resulting from a breakdown of self-tolerance.

Molecular mimicry — a microbial antigen resembles a self antigen, so the response cross-reacts. Streptococcal M protein and cardiac myosin in rheumatic fever; Campylobacter jejuni and peripheral nerve gangliosides in Guillain-Barré syndrome
Release of sequestered antigen — antigens hidden from the immune system during development are seen as foreign when released: sympathetic ophthalmia after penetrating eye injury, and antisperm antibodies after vasectomy
Failure of regulatory T cells or loss of anergy, and polyclonal activation by superantigens, infections and drugs
Alteration of self antigen by drugs, as in drug-induced lupus (hydralazine, procainamide, isoniazid) and drug-induced haemolysis (methyldopa)
Genetic predisposition — strong HLA associations, familial clustering and a marked female preponderance

CLINICAL PEARL

Rheumatic fever is the clearest demonstration that an infection can cause an autoimmune disease, and that preventing the infection prevents it. Antibody to streptococcal M protein cross-reacts with cardiac myosin, and the valve damage is done by the host response rather than by the organism, which has long since gone. This is why secondary penicillin prophylaxis works: it prevents the recurrent infections that would provoke further attacks — a major programme in India, where rheumatic heart disease remains common.

Classification of Autoimmune Disease

Type	Features	Examples
Organ-specific	Antigen confined to one organ; damage limited to it; antibodies are organ-specific	Hashimoto thyroiditis and graves disease; type 1 diabetes; pernicious anaemia; myasthenia gravis; Addison disease; autoimmune haemolytic anaemia; goodpasture syndrome; vitiligo; pemphigus
Non-organ-specific (systemic)	Antigen widely distributed; multiple organs affected; often immune-complex mediated	SLE, rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, polymyositis, the vasculitides
Intermediate	Features of both	Primary biliary cholangitis, autoimmune hepatitis

Autoantibodies of Diagnostic Value

Antibody	Disease
Antinuclear (ANA)	SLE — highly sensitive (a negative test makes SLE very unlikely) but not specific; positive in many conditions and in some healthy people
Anti-double-stranded DNA; anti-Smith	SLE — highly specific; anti-dsDNA titre reflects disease activity and nephritis
Rheumatoid factor; anti-CCP	Rheumatoid arthritis. Rheumatoid factor is an IgM against the Fc of IgG and is also positive in chronic infection; anti-CCP is more specific and positive earlier
Anti-thyroid peroxidase; TSH-receptor antibody	Hashimoto thyroiditis; and in graves disease a stimulating ("type V") antibody
Anti-acetylcholine receptor	Myasthenia gravis
Anti-glomerular basement membrane	Goodpasture syndrome (kidney and lung)
ANCA — cANCA (PR3), pANCA (MPO)	Granulomatosis with polyangiitis; microscopic polyangiitis
Anti-tissue transglutaminase, anti-endomysial	Coeliac disease
Anti-mitochondrial; anti-intrinsic factor	Primary biliary cholangitis; pernicious anaemia

Principles of Treatment

Replace what has been lost where the organ is destroyed — thyroxine in Hashimoto disease, insulin in type 1 diabetes, vitamin B12 in pernicious anaemia; immunosuppression is pointless once the tissue has gone
Suppress the immune response where damage is ongoing — corticosteroids, azathioprine, methotrexate, mycophenolate, cyclophosphamide, calcineurin inhibitors
Biological agents targeting specific pathways — anti-TNF, rituximab (anti-CD20), tocilizumab (anti-IL-6R), belimumab, and JAK inhibitors
Remove antibody or complexes — plasmapheresis or intravenous immunoglobulin in Goodpasture syndrome, myasthenic crisis and Guillain-Barré syndrome
Treat the trigger where one exists — penicillin prophylaxis in rheumatic fever, and withdrawal of the offending drug in drug-induced lupus

Applied Aspects

Order autoantibody tests to answer a question, not to screen — ANA is positive in a proportion of healthy people, and an unexplained positive result generates anxiety and unnecessary investigation
A negative ANA makes SLE very unlikely, whereas a positive one requires clinical correlation and more specific tests
Screen for tuberculosis and hepatitis B before immunosuppression, particularly before anti-TNF agents; in India, reactivation is a real and potentially fatal risk
Autoimmune disease clusters in individuals and families; a patient with one organ-specific disease should be assessed for others, especially thyroid and coeliac disease and pernicious anaemia
Rheumatic heart disease remains common in India, and identifying and treating streptococcal sore throat, with lifelong benzathine penicillin prophylaxis after an attack, prevents far more disease than any treatment of established valve damage
Long-term immunosuppression carries cumulative harm, so the aim is the lowest effective burden with steroid-sparing agents introduced early

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