Identification of new immune subtypes of renal injury associated with anti-neutrophil cytoplasmic antibody-associated vasculitis based on integrated bioinformatics analysis

Lizhen Lin; Keng Ye; Fengbin Chen; Jingzhi Xie; Zhimin Chen; Yanfang Xu

doi:10.3389/fgene.2023.1119017

Identification of new immune subtypes of renal injury associated with anti-neutrophil cytoplasmic antibody-associated vasculitis based on integrated bioinformatics analysis

Front Genet. 2023 Apr 5:14:1119017. doi: 10.3389/fgene.2023.1119017. eCollection 2023.

Authors

Lizhen Lin¹, Keng Ye^{2

3

4}, Fengbin Chen¹, Jingzhi Xie^{2

3

4}, Zhimin Chen^{2

3

4}, Yanfang Xu^{2

3

4

5}

Affiliations

¹ Department of Traditional Chinese Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
² Blood Purification Research Center, Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
³ Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
⁴ National Regional Medical Center, Department of Nephrology, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
⁵ Central Laboratory, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

Abstract

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that may lead to end-stage renal disease. However, few specifific biomarkers are available for AAV-related renal injury. The aim of this study was to identify important biomarkers and explore new immune subtypes of AAV-related renal injury. Methods: In this study, messenger RNA expression profiles for antibody-associated vasculitis and AAV-associated kidney injury were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes to AAV. Key module genes from WGCNA were then intersected with AAV- and nephropathy-related genes from the Genecards database to identify key genes for AAV-associated kidney injury. Subsequently, the expression of key genes was validated in independent datasets and the correlation of genes with clinical traits of kidney injury was verified by the Nephroseq database. Finally, non-negative matrix factorization (NMF) clustering was performed to identify the immune subtypes associated with the key genes. Results: Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identifified, and validated the expression levels independent datasets. Receiver operating characteristic curve analysis revealed that these eight genes have major diagnostic value as potential biomarkers of AAV-related renal injury. Through our comprehensive gene enrichment analyses, we found that they are associated with immune-related pathways. NMF clustering of key genes identified two and three immune-related molecular subtypes in the glomerular and tubular data, respectively. A correlation analysis with prognostic data from the Nephroseq database indicated that the expression of co-key genes was positively co-related with the glomerular filtration rate. Discussion: Altogether, we identifified 8 valuable biomarkers that firmly correlate with the diagnosis and prognosis of AAV-related renal injury. These markers may help identify new immune subtypes for AAV-related renal injury.

Keywords: ANCA-associated vasculitis; WGCNA; bioinformatics; biomarkers; immune subtypes; renal injury.

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (No. 82070720), Fujian Provincial Health Technology Project (No. 2021ZQNZD004), Fujian Province Traditional Chinese Medicine Research Project (No. 2021zyjc09) and Fujian Province Finance Project (2020B009). YX was supported by Fujian Research and Training Grants for Young and Middle_aged Leaders in Healthcare.