Reduced B cell frequencies in cord blood of HIV-exposed uninfected infants: an immunological and transcriptomic analysis

Jin, Ye1,2; Zhao, Jun3; Qi, Tangkai1; Tian, Di4; Liao, Yixin4; Yang, Qing5; Li, Minming1; Zhu, Qingqing5; Chen, Jun1,4; Shen, Yinzhong1,4; Liu, Yabin4; Lu, Hongzhou1,4,6

2024-09-04

10.3389/fimmu.2024.1445239

FRONTIERS IN IMMUNOLOGY   影响因子和分区

1664-3224

Introduction: In the course of immune development, HIV-exposed uninfected (HEU) infants exhibit abnormal immune function and increased infectious morbidity compared to HIV-unexposed uninfected (HUU) infants. Yet the specific functional phenotypes and regulatory mechanisms associated with in-utero HIV and/or ART exposure remain largely obscure. Methods: We utilized flow cytometry and RNA-seq technologies to conduct the immunological and transcriptomic 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 unique effects induced by in-utero HIV and/or ART exposure. Results: Flow cytometry immunophenotyping revealed that the level of B lymphocyte subsets was significantly decreased in HEU cord blood as compared to HUU (P < 0.001). Expression profiling-based cell abundance assessment, includes CIBERSORT and ssGSEA algorithm, showed a significantly reduced abundance of naive B cells in HEU cord blood (both P < 0.05), supporting the altered composition of B lymphocyte subsets in HEU. Functional enrichment analysis demonstrated suppressed innate immune responses and impaired immune regulatory function of B cells in HEU cord blood. Furthermore, through differential expression analysis, co-expression network analysis using WGCNA, and feature selection analysis using LASSO, we identified a 4-gene signature associated with HEU status. This signature effectively assesses B cell levels in cord blood, enabling discrimination between HEU and HUU infants. Discussion: Our study provides the first comprehensive immunological and transcriptomic characterization of HEU cord blood. Additionally, we establish a 4-gene-based classifier that holds potential for predict immunological abnormalities in HEU infants.

HIV-exposed uninfected cord blood cell counting B lymphocyte transcriptome immune system

SCI

英语

通讯

Clinical Research Project of Shanghai Public Health Clinical Center[KY-GW-2023-02] ; Jinshan District Medical Health Science and Technology Innovation Fund Project[2023-WS-05] ; Key Discipline Program on Public Health System Construction of Shanghai[GWVI-11.1-09] ; Scientific Research Project of Shanghai Municipal Health Commission[202140486] ; Shanghai Hospital Development Center Foundation[SHDC12022121] ; National Natural Science Foundation of China["82072281","92169119"] ; Shanghai Municipal Science and Technology Major Project[ZXS004R1-2]

Immunology

Immunology

WOS:001315401700001

FRONTIERS MEDIA SA

Web of Science

1.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Dept Infect & Immunol, Shanghai, Peoples R China
2.Shanghai Ctr Women & Childrens Hlth, Childrens Hlth Dept, Shanghai, Peoples R China
3.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Dept Pediat, Shanghai, Peoples R China
4.Fudan Univ, Sci Res Ctr, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China
5.Songjiang Matern & Child Hlth Hosp, Child Healthcare Dept, Shanghai, Peoples R China
6.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen, Peoples R China

Jin, Ye,Zhao, Jun,Qi, Tangkai,et al. Reduced B cell frequencies in cord blood of HIV-exposed uninfected infants: an immunological and transcriptomic analysis[J]. FRONTIERS IN IMMUNOLOGY,2024,15.

Jin, Ye.,Zhao, Jun.,Qi, Tangkai.,Tian, Di.,Liao, Yixin.,...&Lu, Hongzhou.(2024).Reduced B cell frequencies in cord blood of HIV-exposed uninfected infants: an immunological and transcriptomic analysis.FRONTIERS IN IMMUNOLOGY,15.

Jin, Ye,et al."Reduced B cell frequencies in cord blood of HIV-exposed uninfected infants: an immunological and transcriptomic analysis".FRONTIERS IN IMMUNOLOGY 15(2024).