INVOLVEMENT OF ANTILIPOARABINOMANNAN ANTIBODIES IN CLASSICAL COMPLEMENT ACTIVATION IN TUBERCULOSIS

We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculos is products. After exposure to BCG, there were higher levels of the te rminal complement complex in sera from Indian tuberculosis patients th an in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical act ivation. Sera from Indian tuberculosis patients contained more antibod y to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated p ositively with classical activation induced by BCG in the sera. By flo w cytometry, deposition of C3 and terminal complement complex on bacil li incubated with normal human serum was demonstrated. The anticomplem ent staining was significantly reduced in the presence of EGTA and EDT A. Flow cytometry also revealed the binding of complement to BCG incub ated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement a ctivation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be imp ortant for the extent of phagocytosis of M. tuberculosis by mononuclea r phagocytes, which may influence the course after infection.