Autoimmunity

Definition

Autoimmunity - loss of self-tolerance, leading the immune system to attack the body's own tissue - the shared mechanism underlying a wide range of organ-specific and systemic diseases
Autoimmune disease collectively affects ~5-8% of the population; most individual autoimmune conditions show F>M predominance, particularly during reproductive years, pointing to a hormonal contribution

Central tolerance - self-reactive T cells deleted in the thymus (negative selection), B cells in the bone marrow; incomplete deletion allows some autoreactive clones to escape
Peripheral tolerance - regulatory T cells (Tregs), anergy, and immune privilege sites normally suppress escaped autoreactive clones - breakdown here is the final step before overt disease
Molecular mimicry - a pathogen antigen structurally resembles a self-antigen, and the immune response generated against the pathogen cross-reacts with self-tissue (e.g. rheumatic fever, Guillain-Barre syndrome)
Epitope spreading - an initially narrow autoimmune response broadens over time to target additional self-antigens, explaining progressive multi-antigen involvement in chronic autoimmune disease

Autoantibody panels (ANA, ENA, ANCA, organ-specific antibodies) support diagnosis but require clinical correlation - low-titre autoantibodies are common in health, especially with advancing age

Management is disease-specific, but broadly spans immunosuppression targeting the dysregulated response (corticosteroids, steroid-sparing agents, biologics) rather than curing the underlying tolerance defect

Rheumatoid arthritis, SLE, type 1 diabetes, multiple sclerosis, autoimmune thyroid disease - genetic susceptibility (HLA associations) plus environmental trigger is the common causal model across most autoimmune disease
Autoimmune diseases cluster - a patient with one autoimmune condition has an increased risk of developing another, consistent with a shared underlying susceptibility to tolerance breakdown rather than each disease being an independent event

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