ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY IN SYSTEMIC LUPUS-ERYTHEMATOSUS

Abstract

Serum factors activating the alternative pathway of complement [C] in vitro, independent of classical pathway activation were demonstrated in 6 of 11 patients with systemic lupus erythematosus (SLE). These serum factors were detected by lysis of gluthathione-sensitized human erythrocytes and by C3 [the 3rd C component] and factor B conversion in the presence of EGTA (10 mM) and MgCl2 (0.3 mM), conditions which blocked activation of the classical pathway but permitted activation of the alternative pathway. To determine if in vivo activation of the alternative pathway was present in SLE, highly-purified factor B was labeled with 125I and its metabolism studied in the 11 patients with SLE and in 12 control subjects. 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 increased fractional catabolic rate (FCR) of factor B. Two patients without demonstrable alternative pathway activating factors in their sera had an elevated FCR of factor B. Six of the patients with increased FCR of factor B had disease limited to skin or joint, and 1 had lupus nephritis which was inactive at the time of study. One of the 4 patients who were in clinical remission had elevated FCR. A significant number of patients with SLE of relatively mild disease activity had evidence of alternative complement pathway activation. This activation did not appear limited to patients with lupus nephritis, and the possibility was raised that it could also be related to some of the extra-renal manifestations of SLE.