# Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren’s syndrome based on comprehensive bioinformatics and immunohistochemical analyses

## TL;DR

This study explores shared genes and immune pathways in IgA nephropathy and Sjögren’s syndrome to uncover their molecular crosstalk and potential treatment targets.

## Contribution

The study identifies crosstalk genes and immune cell patterns common to IgA nephropathy and Sjögren’s syndrome using bioinformatics and immunohistochemistry.

## Key findings

- 28 commonly up-regulated genes and 98 module genes were identified between IgA nephropathy and Sjögren’s syndrome.
- Five hub genes (PSMB8, PSMB9, IFI44, ISG15, CD53) were validated through immunohistochemistry and external validation.
- Effector memory CD8 T and T follicular helper cells were significantly activated in both diseases.

## Abstract

IgA nephropathy (IgAN) and Sjogren's syndrome (SS) are two autoimmune diseases with undetermined etiology and related to abnormal activation of lymphocytes. This study aims to explore the crucial genes, pathways and immune cells between IgAN and SS. Gene expression profiles of IgAN and SS were obtained from the Gene Expression Omnibus and Nephroseq data. Differentially expressed gene (DEG) and weighted gene co-expression network analyses (WGCNA) were done to identify common genes. Enrichment analysis and protein–protein interaction network were used to explore potential molecular pathways and crosstalk genes between IgAN and SS. The results were further verified by external validation and immunohistochemistry (IHC) analysis. Additionally, immune cell analysis and transcription factor prediction were also conducted. The DEG analysis revealed 28 commonly up-regulated genes, while WGCNA identified 98 interactively positive-correlated module genes between IgAN and SS. The enrichment analysis suggested that these genes were mainly involved in the biological processes of response to virus and antigen processing and presentation. The external validation and IHC analysis identified 5 hub genes (PSMB8, PSMB9, IFI44, ISG15, and CD53). In the immune cell analysis, the effector memory CD8 T and T follicular helper cells were significantly activated, and the corresponding proportions showed positively correlations with the expressions of the 5 hub genes in the two autoimmune diseases. Together, our data identified the crosstalk genes, molecular pathways, and immune cells underlying the IgAN and SS, which provides valuable insights into the intricate mechanisms of these diseases and offers potential intervention targets.

The online version contains supplementary material available at 10.1007/s10238-024-01420-1.