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.