IgA immunity in HIV type 1-infected chimpanzees. I. Systemic immunity.

Abstract

HIV infection in humans causes various aberrancies in both the cellular and humoral immune systems, including functional abnormalities of B lymphocytes. In many instances, dysfunction occurs in the regulation of serum IgA, resulting in elevated concentrations of this immunoglobulin isotype. To determine whether HIV-1-infected chimpanzees develop IgA abnormalities similar to those observed in humans, we quantified total IgA, IgG, and IgM levels in sera collected longitudinally from six HIV-infected chimpanzees and one uninfected control animal. In comparison to immunoglobulin levels in the uninfected animal, two of the six infected chimpanzees exhibited increases in serum immunoglobulins following infection with HIV. Two other infected animals showed a marked decrease in the three isotypes within 10 months of exposure to HIV, followed by a return to baseline levels. The remaining two HIV-infected chimpanzees displayed serum immunoglobulin levels that paralleled the baseline levels and did not show great deviation over a period of 20 to 45 months postinfection. ELISA analyses of the IgA subclasses revealed possible abnormalities of the IgA2 subclass within the two animals that did not display irregular IgA, IgG, or IgM responses to HIV-1. Specific IgG, IgA, IgA1, and IgA2 antibodies to HIV antigens were detected by an enzyme immunoassay (EIA) kit and by Western blot analysis with IgA, IgA1, and IgA2 antibodies directed against the env, gag, and pol gene products. Because IgG can mask the detection of HIV-specific IgA antibodies in infected humans, Western blots and EIAs were also performed on IgG-depleted chimpanzee sera. The results demonstrated that in some instances, IgA reactivity against HIV antigens can be enhanced on removal of IgG. This study indicates that HIV-1 is capable of inducing abnormalities in serum IgA expression in chimpanzees. These results might further understanding of how HIV affects humoral responses in infected humans.