INHIBITION OF CLASSICAL COMPLEMENT ACTIVATION BY SERA FROM HIV-1-POSITIVE PATIENTS

It was shown that gp120/160-coupled CD4(+) T cells could be lysed by c omplement activation, but the target cell lysis was strongly inhibited by the majority of HIV-1-positive sera. Significantly more sera from HIV-1-infected patients with CD4(+) T cell count higher than 500 mu l (N = 38) as well as from patients with 200-500/mu l (N = 32) showed st rong inhibition of complement activation as compared to sera from thos e with less than 200 CD4(+) T cells/mu l (N = 28) (P = 0.0064 and 0.00 12, respectively), Consequently, highly significant correlation betwee n CDL inhibitory activity and CD4(+) T cell count in HIV-1-infected pa tients was found by Spearman's rank order analysis (R = 0.399, P < 0.0 01). CH50 titer and functional C1-inhibitor level were significantly l ower in inhibitory as compared to the noninhibitory sera (P < 0.001) a nd to controls (P < 0.001), The C3 activation products-C3-circulating immune complexes were not increased in inhibitory sera (P = 0.014) sug gesting that inhibition of complement activation occurred at or before C3 activation level. C4d fragments and antigenic C1-INH concentration were significantly increased in both categories of HIV-1-positive ser a, P < 0.001, These findings indicate that persistent and massive stim ulation of complement system with HIV-1 envelope glycoproteins during all stages of the disease induced impairment of classical pathway acti vation by an inhibitory factor in a majority of patients, which might contribute to the onset of opportunistic infections and AIDS. (C) 1996 Academic Press, Inc.