NIH Research Festival
Introduction. HEU infants have a higher risk for adverse metabolic, infectious, and neurodevelopmental outcomes. How HEU immunity is influenced by maternal HIV immune status is understudied, and thus a focus of this study.
Methods. Blood samples obtained from 46 PWH and their HEU newborns pairs were compared to a reference group of 18 pregnant women without HIV (PWOH) and their HIV-unexposed uninfected (HUU) neonates. HEU infants were evaluated at birth and 6 months along with a longitudinal cohort of 32 HUU infants. Twenty-one biomarkers associated with B-cell development, macrophage or lymphocyte activation, and inflammation were measured by Mesoscale. The Mann-Whiney and Kruskal-Wallis tests compared two and multiple groups respectively. Spearman‚Äôs test evaluated mother/baby biomarker correlations.
Results. Compared to PWOH, biomarkers related to B-cell development (sCD40L, IL-21), immune activation (sCD163, sCD27, IL-22), and inflammation (CXCL9, CXCL10, CCL5, TNF-Œ±, IL-1Œ≤) elevated significantly in PWH. In contrast, APRIL, a biomarker of B-cell development, was lower in PWH. HEU neonates showed significantly higher biomarker concentrations of B-cell development (APRIL, BAFF, sCD40L, IL-21), macrophage activation (sCD14), lymphocyte activation (sCD27, IFN-Œ≥, IL-22), inflammatory (CXCL9, CCL4, CCL5, CXCL8, TNF-Œ±, IL-1Œ≤, IL-6), and anti-inflammatory (IL-10, IL-1RA) compared to HUU newborns, which persisted through 6 months of life. Among PWOH and PWH mother/neonate pairs there was a positive correlation in BAFF, IL-21, sCD14, IL-17A, and CXCL9. PWH/HEU newborns dyads displayed additional positive correlations in APRIL, sCD163, IFN-Œ≥, CXCL10, CCL4, CCL5, TNF-Œ±, IL-1Œ≤, IL-6, and IL-1RA.
Conclusions. HEU infants have impaired early immune priming influenced by maternal immune perturbations.
Scientific Focus Area: Virology
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