Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis

Xianxian Jia; Hua Zhu; Qinglian Jiang; Jia Gu; Shihan Yu; Xuyang Chi; Rui Wang; Yu Shan; Hong Jiang; Xiaoxue Ma

doi:10.3389/fimmu.2023.1087293

Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis

Front Immunol. 2023 Mar 21:14:1087293. doi: 10.3389/fimmu.2023.1087293. eCollection 2023.

Authors

Xianxian Jia¹, Hua Zhu¹, Qinglian Jiang^{1

2}, Jia Gu¹, Shihan Yu¹, Xuyang Chi¹, Rui Wang¹, Yu Shan³, Hong Jiang¹, Xiaoxue Ma^{1

4}

Affiliations

¹ Department of Pediatrics, The First Hospital of China Medical University, Shenyang, China.
² Department of General Pediatrics, Zhongshan City People's Hospital, Guangzhou, China.
³ First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁴ Department of Microbiology & Immunology and Pediatrics, Dalhousie University, Halifax, NS, Canada.

Abstract

Background: IgAV, the most common systemic vasculitis in childhood, is an immunoglobulin A-associated immune complex-mediated disease and its underlying molecular mechanisms are not fully understood. This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN.

Methods: GSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN.

Result: A total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN.

Conclusion: We screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.

Keywords: bioinformatics analysis; differentially expressed genes; hub genes; immune infiltration; immunoglobulin A associated vasculitis nephritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Databases, Factual
Humans
IgA Vasculitis* / genetics
Immune Complex Diseases*
Immunoglobulin A

Substances

Immunoglobulin A

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant 81901658); Liaoning Province Natural Science Foundation (2022-BS-134); Infection, Immunity, Inflammation & Vaccinology (I3V) Dalhousie Medical Research Foundation (DMRF) Dr. David H. Hubel Program.