Semen IgM, IgG1, and IgG3 Differentially Associate With Pro-Inflammatory Cytokines in HIV-Infected Men

Genital inflammation significantly increases the risk for HIV infection. The seminal environment is enriched in pro-inflammatory cytokines and chemokines. Here, we investigated the interplay between semen cytokines and humoral immunity to understand whether the characteristics of semen antibodies are associated with genital inflammation. In 36 HIV-infected and 40 HIV-uninfected mens’ semen, HIV-specific antibodies (gp120, gp41, p66 and p24), immunoglobulin (Ig) subclasses, isotypes and cytokines, using multiplex assays, were measured. Semen IgG1, IgG3 and IgM were significantly higher in HIV-infected compared to HIV-uninfected men (p0.55; p-0.65, p0.44, p<0.03), while p24 antibodies correlated significantly with chemokine MIP-1β (r=0.451; p=0.024). Local cytokines/chemokines were associated with the mucosal-specific Ig subclasses which likely effect specific antibody functions. Together, these data inform on mucosal-specific immunity that may be elicited in the male genital tract in future vaccines and/or combination HIV prevention strategies.