In a study population representing different CDC stages of
HIV infection, 58% exhibited
IgA hypergammaglobulinemia resulting from proportional increases in both the
IgA1 and the
IgA2 subclasses. These increases were detected early in
infection, did not correlate with CD4 count, and remained elevated throughout
disease progression. Absolute concentrations of
polymeric IgA present within each subclass were unchanged, indicating that increased production of monomeric
IgA1 and
IgA2 were responsible for elevations of total
IgA. These elevations were not completely attributable to a specific antibody response to
viral infection, since Western blot analysis of purified
IgA samples indicated that HIV-reactive
IgA antibodies could be demonstrated only within the
IgA1 subclass. Dominating
IgA1 anti-HIV responses were also observed in two
secretory IgA samples isolated from colostrum of healthy HIV seropositive mothers, suggesting that a similar isotype restriction exists in the mucosal
IgA compartment. The binding of
IgA1 to
HIV proteins contrasted markedly to that observed with identical concentrations of
IgG purified from the sera of the same patients. While
IgG reacted more intensely and broadly with all
HIV proteins,
IgA1 antibodies were directed predominantly against envelope
glycoproteins. In many patients, a total lack of
IgA1 reactivity to gag and pol
proteins was accompanied by intact
IgG responses to these same
antigens. Though all
IgA samples examined reacted with HIV, fewer responses to gp160, gp120, and p24 were observed in samples from
AIDS and
AIDS-related complex (
ARC) patients, suggesting a declining titer of
IgA antibodies against these
antigens may be associated with
disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)