Potential common molecular mechanisms between Sjögren syndrome and inclusion body myositis: a bioinformatic analysis and in vivo validation

Li Zeng; Kai Chen; Feng Xiao; Chun-Yan Zhu; Jia-Ying Bai; Song Tan; Li Long; Yi Wang; Qiao Zhou

doi:10.3389/fimmu.2023.1161476

Potential common molecular mechanisms between Sjögren syndrome and inclusion body myositis: a bioinformatic analysis and in vivo validation

Front Immunol. 2023 Apr 21:14:1161476. doi: 10.3389/fimmu.2023.1161476. eCollection 2023.

Authors

Li Zeng¹, Kai Chen¹, Feng Xiao¹, Chun-Yan Zhu¹, Jia-Ying Bai¹, Song Tan^{1

2}, Li Long³, Yi Wang⁴, Qiao Zhou^{3

5}

Affiliations

¹ Department of Neurology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
² Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, Chengdu, China.
³ Department of Rheumatology and Immunology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁴ Department of Critical Care Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Background: Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren's syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach.

Methods: IBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein-protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network.

Results: Using WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs.

Conclusion: Our study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association.

Keywords: Sjögren syndrome; antigen processing and presentation; bioinformatic analysis; immune infiltration landscape; inclusion body myositis; viral infection.

Publication types

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

MeSH terms

Antigen Presentation
Autoimmune Diseases*
Computational Biology
Humans
Myositis, Inclusion Body* / genetics
Sjogren's Syndrome* / genetics

Grants and funding

This study received funding support from the National Natural Science Foundation of China (Code: 81801270, 81802504), International Cooperation Program of Sichuan Science and Technology Bureau (2022YFH0005, 2023YFH0010, 2020JDJQ0067), the Science and Technology Innovation Project of Chengdu, China (No. 2021-YF05-00225-SN), Sichuan Medical Association grant (No. Q19037).