Patients with complement deficiencies may also develop a variety of rheumatic diseases. These include a disorder that resembles systemic lupus erythematosus (SLE) as well as glomerulonephritis, dermatomyositis, anaphylactoid purpura and vasculitis. The prevalence of these inflammatory disorders is highest in those patients with deficiencies of the classical activating pathway (C1, C4 and C2) and of C3. For example, approximately 80% of patients with C4 or C3 deficiency diseases and just over 30% of patients with C2 deficiency have had a rheumatic disorder. In contrast, fewer than 10% of patients with deficiencies of terminal complement components have rheumatic disorders. The most attractive hypothesis linking rheumatic diseases and complement deficiency diseases has to do with the role of the complement system in the clearance and processing of immune complexes. A number of studies have shown that the sera of patients with complement deficiencies have altered and/or reduced abilities to process immune complexes and that the inability of the patients’ sera to process immune complexes in vitro correlates with their risk for developing a rheumatic disorder. For example, serum from patients with genetically determined deficiencies of C1, C4, C2 and C3 fails to prevent the precipitation of immune complexes as they are forming, has a reduced ability to resolubilize complexes once they have formed, and does not support the binding of preformed immune complexes to C3b receptors on human erythrocytes. In contrast, the serum of patients with deficiencies of terminal components (C5–C9) are normal with respect to these activities.
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