What are the rheumatologic manifestations of homozygous complement deficient states?
Deficiencies of the early components of the classic pathway (C1, C4, and C2) are associated with immune complex disease, particularly SLE or a lupus-like glomerulonephritis. Dermatomyositis, vasculitis, and others have also been described. This may be due to impaired clearance of apoptotic cells, inability to maintain circulating immune complexes in a soluble state, and/or inability to remove circulating immune complexes. The reported prevalence of SLE is 93% with C1q, 75% with C4, and 33% with C2 deficiency. C2 deficiency is the most common complement deficiency (1 in 20,000 individuals).
Factor H deficiency as well as polymorphisms have been associated with atypical (diarrhea-negative) hemolytic-uremic syndrome and glomerulonephritis. A similar syndrome may occur with factor I and MCP defects. These patients may be helped by treatment with eculizumab (Soliris). Since factor H deficiency can also lead to secondary C3 deficiency, patients may be at increased risk for infections.
