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Participation of the Alternative Pathway in Complement Metabolism in Systemic Lupus Erythematosus

Division of Allergy and Immunology, Scripps Clinic and Research Foundation, La Jolla, Calif

Abstract

In order to determine if in vivo activation of the alternative pathway of complement was present in systemic lupus erythematosus (SLE), highly-purified Factor B was labeled with radioactive iodine (¹²⁵I), and its metabolism studied in 11 patients with SLE and 6 control subjects. Serum factors, which could activate the alternative pathway of complement in in vitro assays were demonstrated in 6 of 11 patients with SLE. These serum factors were detected by lysis of glutathione-sensitized human erythrocytes and by C3 and Factor B conversion in the presence of EGTA (10 mM) and MgCl₂ (0.3 mM) conditions which block activation of the classical pathway but permit activation of the alternative pathway. All 6 patients with serum factors capable of activating the alternative pathway in vitro, had in vivo evidence of alternative pathway activation as measured by an increased fractional catabolic rate (FCR) of Factor B.