Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link

Jianbo Qing; Xueli Hu; Changqun Li; Wenzhu Song; Hasna Tirichen; Hasnaa Yaigoub; Yafeng Li

doi:10.3389/fimmu.2022.929138

Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link

Front Immunol. 2022 Aug 17:13:929138. doi: 10.3389/fimmu.2022.929138. eCollection 2022.

Authors

Jianbo Qing^{1

2}, Xueli Hu³, Changqun Li¹, Wenzhu Song³, Hasna Tirichen⁴, Hasnaa Yaigoub⁴, Yafeng Li^{2

5

6

7}

Affiliations

¹ The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, China.
² Department of Nephrology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China.
³ School of Public Health, Shanxi Medical University, Taiyuan, China.
⁴ Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China.
⁵ Core Laboratory , Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China.
⁶ Shanxi Provincial Key Laboratory of Kidney Disease, Taiyuan, China.
⁷ Academy of Microbial Ecology, Shanxi Medical University, Taiyuan, China.

Abstract

Background: IgA nephropathy (IgAN) is an autoimmune disease that affects people of any age and is an important cause of end-stage renal disease. However, the pathogenesis and pathophysiology of IgAN is not clear. This article aimed to explore the immune-mediated inflammation and genetic mechanisms in IgAN.

Methods: The transcriptome sequencing data of IgAN glomeruli in the Gene Expression Omnibus database were downloaded. Single-sample gene set enrichment analysis was used to estimate the immune microenvironment of the merged microarray data and GSE141295. IgAN samples were divided into two clusters by cluster analysis. "limma" and "DEseq2" package in R were used to identify differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules related to inflammation in IgAN. R software package "clusterProfiler" was used for enrichment analysis, whereas Short Time-Series Expression Miner (STEM) analysis was used to identify the trend of gene expression. Machine-learn (ML) was performed using the shiny app. Finally, Drug Signatures Database (DSigDB) was used to identify potential molecules for treating IgAN.

Results: The infiltration of macrophages in IgAN glomeruli was increased, whereas CD4+ T cells, especially inducedregulatory T cells (iTregs) were decreased. A total of 1,104 common DEGs were identified from the merged data and GSE141295. Brown module was identified to have the highest inflammatory correlation with IgAN using WGCNA, and 15 hub genes were screened from this module. Among these 15 hub genes, 14 increased with the severity of IgAN inflammation based on STEM analysis. Neural network (nnet) is considered as the best model to predict the severity of IgAN. Fucose identified from DSigDB has a potential biological activity to treat IgAN.

Conclusion: The increase of macrophages and the decrease of iTregs in glomeruli represent the immune-mediated inflammation of IgAN, and fucose may be a potential therapeutic molecule against IgAN because it affects genes involved in the severe inflammation of IgAN.

Keywords: IgA nephropathy; fucose; hub genes; immune-mediated inflammation; machine learning.

Publication types

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

MeSH terms

Fucose
Gene Expression Profiling*
Glomerulonephritis, IGA* / drug therapy
Glomerulonephritis, IGA* / genetics
Glomerulonephritis, IGA* / metabolism
Humans
Immunoglobulin A / genetics
Inflammation / genetics

Substances

Immunoglobulin A
Fucose