Department of Infection Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Children's Health Department, Shanghai Center for Women and Children's Health, Shanghai, China.
Front Immunol. 2024 Sep 4;15:1445239. doi: 10.3389/fimmu.2024.1445239. eCollection 2024.
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 HIV and/or ART exposure remain largely obscure.
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 HIV and/or ART exposure.
Flow cytometry immunophenotyping revealed that the level of B lymphocyte subsets was significantly decreased in HEU cord blood as compared to HUU ( < 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 < 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.
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.
在免疫发育过程中，与未暴露于 HIV 的未感染婴儿（HUU）相比，HIV 暴露未感染婴儿（HEU）表现出异常的免疫功能和更高的传染性发病率。然而，与 HIV 和/或 ART 暴露相关的特定功能表型和调节机制在很大程度上仍不清楚。
我们利用流式细胞术和 RNA-seq 技术对 9 对 HEU 母婴和 24 对 HUU 母婴的脐带血进行免疫和转录组谱分析。此外，我们将脐带血数据集与母体静脉血数据集进行比较，以描述由 HIV 和/或 ART 暴露引起的独特影响。
流式细胞术免疫表型分析显示，与 HUU 相比，HEU 脐带血中 B 淋巴细胞亚群水平显著降低（<0.001）。基于表达谱的细胞丰度评估，包括 CIBERSORT 和 ssGSEA 算法，显示 HEU 脐带血中幼稚 B 细胞丰度显著降低（均<0.05），支持 HEU 中 B 淋巴细胞亚群组成的改变。功能富集分析表明，HEU 脐带血中先天免疫反应受到抑制，B 细胞免疫调节功能受损。此外，通过差异表达分析、使用 WGCNA 的共表达网络分析以及使用 LASSO 的特征选择分析，我们确定了与 HEU 状态相关的 4 个基因特征。该特征可有效评估脐带血中的 B 细胞水平，能够区分 HEU 和 HUU 婴儿。
我们的研究首次全面描述了 HEU 脐带血的免疫学和转录组学特征。此外，我们建立了一个基于 4 个基因的分类器，该分类器具有预测 HEU 婴儿免疫异常的潜力。
