The Hereditary and Acquired Deficiencies of Complement

Abstract

The identification of hereditary and acquired complement deficiencies in humans has led to a better understanding of the biologic importance of the complement system in immunity and autoimmune disease. Although the understanding of the relevance of complement in the pathogenesis of disease is incomplete, several characteristic clinical syndromes associated with complement deficiencies have been recognized and should be known to the practicing clinician. In allergic diseases, one need recognize the C1 inhibitor deficiency syndromes which can present as severe, recurrent angioedema in childhood or in the adult as recurrent angioedema in association with a lymphoid malignancy or autoimmune disease. Complement analyses allow one to readily diagnose C1 inhibitor deficiency in angioedema. Correct diagnosis is critical because safe effective therapy is available. Chronic urticaria is also uncommonly associated with complement deficiencies, particularly acquired C1q deficiency. Again, effective therapy for hypocomplementemic urticarial vasculitis and C1q deficiency is available and differs significantly from the usual management of chronic urticaria. Homozygous and acquired deficiencies of C3 are associated with severe immune deficiency and recurrent infections with gram-positive and gram-negative bacteria. Recurrent meningococcemia and gonococcemia are being identified frequently in patients with a deficient membrane attack mechanism relating to deficiency of C5, C6, C7, or C8. Nearly one third of the patients developing meningococcemia may have an associated complement deficiency indicating the importance of complement determinations in understanding the treatment and prognosis for these patients. Deficiency of almost every complement component has been reported in association with one or more rheumatic diseases, particularly systemic lupus erythematosus. Extensive studies of C2 deficiency and limited studies of C4 deficiency indicate that these components of the classical pathway of complement are important in preventing the development of SLE or are linked to other genes predisposing to SLE. The clinical presentations of SLE in association with C2 or C4 deficiency are relatively uniform. The patients exhibit typical skin manifestations suggestive of SLE and DLE and often exhibit antibodies to SSA (Ro). The association of complement deficiencies with clinical syndromes is important for today's physician. The syndromes and deficiencies described here are the beginning of an expanding knowledge relating to the pathobiology of complement in human disorders.