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

INTRODUCTION

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 trajectories in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children, and (iii) cytokine groupings. Additionally, we explored the impact of the timing of maternal antiretroviral treatment (ART) initiation on cytokine levels and if cytokines predicted repeated hospitalisations during the first two years of life.

METHODS

We assessed 399 mother-child pairs in the Drakenstein Child Health Study, mothers in pregnancy (n = 179 with HIV and n = 220 without HIV) and their children at 7 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 immune trajectories with mixed models. Cytokine patterns were identified using principal component analysis integrated with an ANOVA framework, and associations with hospitalisations were analysed using mixed-effects logistic regression.

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 than 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. ART initiation during compared to before pregnancy, was associated with higher maternal immune markers but not in children. Lower MMP-9 in mothers with HIV and lower MMP-9 and IL-10 in HEU and higher NGAL levels in HUU children predicted increased likelihood of repeated hospitalisations.

CONCLUSIONS

Altered immune responses are present in mothers living with HIV that persist longitudinally in their HEU children, potentially contributing to their health outcomes.