Principles of innate and adaptive immune responses

Two arms in rheumatic disease

Rheumatic disease pathogenesis involves both innate (immediate, non-specific) and adaptive (antigen-specific, memory-generating) immune system components, with the relative contribution of each varying by specific disease - understanding this split informs why different diseases respond to different targeted therapies
Applies across essentially the full spectrum of rheumatic disease, from predominantly innate-driven conditions (gout, some autoinflammatory syndromes) to predominantly adaptive/autoantibody-driven conditions (SLE, RA)

Innate immunity (macrophages, neutrophils, NK cells, complement, inflammasome activation) provides immediate, pattern-recognition-based responses - dominant in gout (crystal-triggered NLRP3 inflammasome activation) and the autoinflammatory syndromes (e.g. familial Mediterranean fever), which lack the autoantibodies/autoreactive T cells characteristic of classic autoimmune disease
Adaptive immunity (autoreactive T cells, autoantibody-producing B cells/plasma cells) drives classic autoimmune rheumatic disease - RA (citrullinated protein-directed autoimmunity, rheumatoid factor/anti-CCP), SLE (autoantibodies against nuclear antigens), and most vasculitides

This distinction is reflected in nomenclature: autoinflammatory disease (innate-driven, no autoantibodies, e.g. familial Mediterranean fever, gout) vs autoimmune disease (adaptive-driven, with autoantibodies/autoreactive lymphocytes, e.g. SLE, RA) - though many diseases show genuine overlap between the two categories rather than falling cleanly into one or the other

Treatment targeting reflects this split: IL-1 blockade (anakinra, canakinumab) targets innate/inflammasome-driven disease (autoinflammatory syndromes, some gout); B cell depletion (rituximab) and T cell-targeted therapy target adaptive-driven autoimmune disease
Recognising which arm predominates in a specific disease guides both diagnostic expectations (autoantibody positivity likely in adaptive-driven disease, unlikely in purely autoinflammatory disease) and treatment selection

Familial Mediterranean fever and other autoinflammatory periodic fever syndromes, gout, rheumatoid arthritis, SLE, NLRP3 inflammasome

The autoinflammatory/autoimmune distinction, while a useful organising framework, is not absolute - some conditions (e.g. some forms of vasculitis) involve genuine contribution from both arms, and treatment sometimes needs to target both pathways together rather than assuming a single dominant mechanism

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