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 complement 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 microl (N = 38) as well as from patients with 200-500/microl (N = 32) showed strong inhibition of complement activation as compared to sera from those with less than 200 CD4+ T cells/microl (N = 28) (P = 0.0064 and 0.0012, respectively). Consequently, highly significant correlation between CDL inhibitory activity and CD4+ T cell count in HIV-1-infected patients was found by Spearman's rank order analysis (R = 0.399, P < 0.001). CH50 titer and functional C1-inhibitor level were significantly lower in inhibitory as compared to the noninhibitory sera (P < 0.001) and to controls (P < 0.001). The C3 activation products-C3-circulating immune complexes were not increased in inhibitory sera (P = 0.014) suggesting 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 sera, P < 0.001. These findings indicate that persistent and massive stimulation of complement system with HIV-1 envelope glycoproteins during all stages of the disease induced impairment of classical pathway activation by an inhibitory factor in a majority of patients, which might contribute to the onset of opportunistic infections and AIDS.
Department of Clinical Immunology, University Hospital of Infectious Diseases Dr Fran Mihaljević, University of Zagreb, Croatia.
V
V
Burek
M
M
Gerenĉer
D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology*; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D015941:Complement Hemolytic Activity Assay; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003171:Complement Pathway, Classical / Q000187:drug effects; D006679:HIV Seropositivity / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
D003174:Complement C1 Inactivator Proteins; D003169:Complement Inactivator Proteins