Maternal and early-life longitudinal cytokine profiles in a South African birth cohort: the impact of HIV.

Background: During pregnancy, exposure to maternal HIV and a disrupted cytokine environment may impact foetal immune development and health outcomes through cytokine-mediated mechanisms. We evaluated (i) peripheral blood cytokine differences in pregnant women with and without HIV, (ii) longitudinal differences in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children, and (iii) latent cytokine groupings. Additionally, we explored the impact of maternal antiretroviral treatment (ART) initiation timing on cytokine levels. Methods: We assessed 399 mother-child pairs in the Drakenstein Child Health Study (DCHS), in pregnancy (n=179 mothers with HIV and n=220 without HIV) and their children at 6 weeks, 2-, 3-, and 5-years. Eighteen serum immune markers were quantified with ELISA and multiplex assays. Group differences were assessed with linear regression, and longitudinal analysis of child immune trajectories was evaluated with linear mixed models. Latent cytokine groupings were assessed using an integrated ANOVA framework with principal component analysis. Results: Pregnant women living with HIV had lower GM-CSF, IL-10, IL-12p70, IL-13, IL-2, IL-4, IL-6, IL-7, NGAL, and MMP-9 levels, and higher TNF-α, IFN-γ, and sCD14 levels compared to women without HIV. HEU children had lower GM-CSF, IL-10, IL-12p70, IL-1β, IL-2, and IL-4 and higher sCD14 levels over time compared to HUU children and revealed distinct immunoregulatory profiles. ART initiation during compared to before pregnancy was associated with higher immune marker levels in mothers but not in their children. Conclusions: Altered immune responses are present in mothers with HIV that persist longitudinally in their HEU children, potentially contributing to their health outcomes.