HIV-1 specificity of cerebrospinal fluid and serum IgG, IgM, and IgG1-G4 antibodies in relation to clinical disease

Abstract

The reactivities of intrathecal and serum IgG and IgM, and IgG1–4 subclass antibodies to various HIV-1 proteins were assessed by immunoblotting at various stages of HIV-1 infection. All patients were examined neurologically including CT and/or MRI, and with HIV-1-specific and nonspecific tests of the cerebrospinal fluid (CSF). In early infection, the occurrence of anti-gag antibodies in both CSF and serum was higher than that of anti-pol antibodies among all IgG subclasses ( P < 0.05). Also in late infection, anti-gag IgG1 response was most frequent ( P < 0.04), while anti-gag IgG3 and IgG4 reactivities predominated over similar anti-pol antibodies ( P < 0.05, respectively). Of anti-pol reactivities, in the CSF of subjects at early infection anti-p32 IgG and IgG1 antibodies were more frequent than in patients at late stages ( P < 0.015). In late infection, however, the occurrence of anti-p64 IgM and IgG2–4 antibodies of both CSF and serum was higher than at early stages ( P = 0.014). Regarding anti-env response, in patients with advanced infection, the CSF and serum IgG subclass reactivity against gp120 was restricted to IgG1. The CSF of individual patients with HIV encephalopathy showed a higher or similar occurrence of polyisotypic anti-gag and anti-pol IgG3 antibodies than corresponding serum. These results indicate association between declining frequency of anti-pol p32 and anti-env gp120 antibodies and severity of HIV-1 disease. On the other hand, the higher occurrence of anti-pol p64 IgM and IgG2-G4 antibodies in both CSF and serum of patients at late infection, indicate active systemic and intrathecal viral replication. Such reactivity of the CSF, in the absence of increased blood-brain barrier permeability, is suggestive of HIV-1 infection the CNS.