Complement Deficiency
Complement deficiency is an inherited deficiency of a component or regulator of the complement system, which increases susceptibility to infection and autoimmune disease. The features depend on which part of the cascade is lost.
Complement deficiencies account for about 1 to 10% of primary immunodeficiencies. Most are autosomal recessive. Properdin deficiency is X-linked. Deficiencies of mannose binding lectin are common but usually have little clinical effect.
Disorders of the classical cascade (C1q, C1r, C1s, C2, C4) cause immune complex disease with a lupus like illness and infections with encapsulated bacteria. C3 deficiency causes severe recurrent pyogenic infection and glomerulonephritis. Terminal component deficiencies (C5 to C9) and properdin or factor D deficiency cause recurrent, often severe, Neisseria infection. Factor H and factor I deficiency cause atypical haemolytic uraemic syndrome and C3 glomerulopathy.
Pathophysiology.
Complement opsonises bacteria, clears immune complexes and apoptotic cells, and forms the membrane attack complex (C5b to C9) that lyses Neisseria. Early classical component deficiency impairs immune complex clearance, which leads to autoimmunity.
Deficiency of C3 prevents opsonisation. Terminal component deficiency leaves opsonisation intact but removes lysis, so only Neisseria is seriously affected. Loss of regulators (factors H and I) causes uncontrolled alternative activation and tissue damage.
