Screening and identification of immunological signatures in cord blood of HIV-exposed uninfected infants
Description
In the course of immune development, HIV-exposed uninfected (HEU) infants exhibit abnormal immune function and higher infectious morbidity compared to HIV-unexposed uninfected (HUU) infants. Yet functional phenotypes and the regulators associated with in-utero HIV exposure remain largely obscure. Herein, we utilized flow cytometry and RNA-seq technologies to establish the immune and transcriptional profiling in cord blood from 9 HEU mother-infant pairs and 24 HUU pairs. On top of that, we compared the cord blood dataset with the maternal venous blood dataset to characterize the unique effects induced by in-utero HIV exposure. Flow cytometry immunophenotyping revealed a significant decrease in the level of B lymphocyte subsets in HEU cord blood compared to HUU cord blood. Expression profiling-based assessment of cell abundance indicated a marked reduction in naive B cells in HEU cord blood, supporting the altered composition of B lymphocyte subsets in HEU infants. Functional enrichment results demonstrated a propensity for suppressed innate immune responses and impaired immune regulatory function of B cells in HEU cord blood. Additionally, through a combination of differential expression analysis, co-expression network analysis, and feature selection analysis, we identified an immunologically significant HEU-related signature. This 4-gene signature could effectively assess B cell levels in cord blood, enabling discrimination between HEU and HUU infants. This study provides the first transcriptomic characterization of HEU cord blood compared to maternal venous blood and establishes a 4-gene-based classifier for predicting immunological abnormalities in HEU infants. These findings hold promise for uncovering new mechanisms underlying abnormal immune system development in infants due to in-utero HIV exposure.