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C4A Deficiency and Elevated Level of Immune Complexes: The Mechanism Behind Increased Susceptibility to Systemic Lupus Erythematosus KRISTÍN H. TRAUSTADOTTIR, ASBJÖRN SIGFUSSON, KRISTJAN STEINSSON, and KRISTJAN ERLENDSSON
ABSTRACT.
Methods. Forty-five healthy individuals having different levels of C4A were studied, 8 with homozygous C4AQ0, 12 with heterozygous C4A deficiency, and 25 with normal C4A. For comparison to the complement status present after prolonged disease activity, 5 patients with SLE homozygous for C4AQ0 were also studied. Results. The results showed that intact immune complex-RBC binding is dependent on the levels of immune complex-bound C3 fragments, which correlate to the levels of IC-bound C4Ad (R = 0.677, p = 0.02), but not on levels of IC-bound total C4d (R = 0.451, p = 0.16). Immune complex binding to RBC was also evaluated in increasing immune complex load. C4A deficient sera had less ability to bind the increased immune complex load to RBC than sera with normal C4A. These results are consistent with the presence of increased amounts of poorly opsonized immune complexes in C4A deficiency, leading to increased precipitation in tissues and initiation of a self-perpetuating cycle. Conclusion. Susceptibility to SLE is increased in individuals with C4A deficiency as C3 opsonization of immune complexes becomes insufficient at elevated immune complex concentrations. (J Rheumatol 2002;29:2359-66) Key Indexing Terms:
COMPLEMENT From the Department of Immunology, Department of Internal Medicine, Division of Rheumatology, and Center for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland. Supported by the Research Fund of the University in Iceland, and the Research Fund of Landspitali-University Hospital. K.H. Traustadottir, MSc; A. Sigfusson, MD, Department of Immunology; K. Steinsson, MD, PhD, Department of Internal Medicine and Center for Rheumatology Research; K. Erlendsson, MD, Associate Professor, Department of Immunology, Department of Internal Medicine. Address reprint requests to Dr. K. Erlendsson, Department of Immunology, Landspitali-University Hospital, 101 Reykjavik, Iceland. E-mail: kristjane@decode.is Submitted November 30, 2001; revision accepted May 10, 2002.
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