Patterns of immunoglobulin G subclass reactivity to HIV-1 envelope peptides in children born to HIV-1-infected mothers

Abstract

Objective: To analyse the pattern of immunoglobulin (Ig) G subclasses specific for HIV-1 envelope peptides in sera from HIV-1-infected mothers and their newborns. We sought to determine whether there was a selective transfer of antibodies from mother to child, and to establish diagnostic or prognostic properties by analysing HIV-1 peptide-specific IgG isotypes.

Design and methods: Parallel sera from 12 HIV-1-infected mothers and their newborn children were analysed for IgG subclass responses to six HIV-1 envelope peptides by enzyme-linked immunosorbent assay. Levels of IgG were compared with levels of IgG1 and IgG3 to an immunodominant gp41 peptide in children's sera obtained during the first months of life. In a longitudinal study of 16 children born to HIV-1-seropositive mothers, of whom 11 were infected, the IgG1 and IgG3 responses to peptides representing an immunodominant epitope of gp41 and the principal neutralizing determinant of the gp120 V3 region were analysed.

Results: IgG1 and IgG3 were found to constitute the predominant peptide-specific antibody responses. A parallel distribution of IgG subclass reactivity was seen in maternal and paediatric sera. There was no evidence of selective antibody transfer. Comparable levels of IgG and IgG1 to the immunodominant peptide were seen in infected and uninfected children, while the IgG3 had disappeared in the majority of uninfected children. A decrease in peptide-specific IgG1 and IgG3 levels was observed in sequential sera from uninfected children, although the kinetic profile varied. Sera from infected children showed de novo synthesis of IgG1 and/or IgG3 binding to the selected HIV-1 peptides. Most children with rapid disease progression failed to produce IgG1 and/or IgG3 to the V3 peptide.

Conclusion: Analysis of IgG subclass kinetics to selected HIV-1 peptides might be a useful additional diagnostic and prognostic tool in evaluating HIV-1 infection in children born to seropositive mothers.