Single-Cell Sequencing Combined with Mendelian Randomization to Explore Potential Diagnostic Biomarkers and Therapeutic Targets for Rheumatoid Arthritis.
TL;DR
It is suggested that B cells play a major role in the RA immune microenvironment and identify CD83 and CRIP2 as potential biomarkers and therapeutic targets and identify probable diagnostic biomarkers as well as therapeutic targets.
Abstract
Background
Rheumatoid Arthritis (RA) is a common autoimmune disease with complex pathogenesis and high prevalence, severely affecting patients' quality of life. Multi-omics analysis has emerged as a powerful tool in RA research, providing insights into cell heterogeneity, genetic mechanisms, and immune microenvironment characteristics. This research looks into important genes linked to rheumatoid arthritis(RA) using single-cell data and Mendelian randomization analysis, while also uncovering the characteristics of the immune microenvironment and its mechanisms linking to these key genes.
Methods
Gene expression, eQTL, and GWAS data were collected. Analyses included single-cell data processing (quality control, dimensionality reduction, clustering, cell annotation, and cell subset contribution assessment), subgroup non-negative matrix factorization, Mendelian randomization, co-localization analysis, immune infiltration analysis, and GSEA/GSVA.
Results
This study analyzed 95,036 single-cell samples and found that alterations in B cells are closely associated with disease progression. Further analysis identified seven distinct B cell subpopulations, with immune responses and the tumor microenvironment exerting significant influence on their dynamics. Mendelian randomization analysis revealed key genes, CD83 and CRIP2, that are linked to the risk of RA. Subsequent investigation demonstrated strong associations between these genes and immune cell populations. GSEA and GSVA analyses showed that CD83 is involved in pathways related to allograft rejection and antigen processing, while CRIP2 is associated with interactions of extracellular matrix receptors and the IL-17 signaling pathway. Additionally, immunometabolism pathway analysis highlighted potential therapeutic targets and underlying mechanisms.
Discussion
The findings suggest that B cells play a major role in the RA immune microenvironment and identify CD83 and CRIP2 as potential biomarkers and therapeutic targets. CD83 may contribute to RA through immune regulation, antigen presentation, and inflammatory signaling, whereas CRIP2 may be involved in metal ion homeostasis, cellular stress responses, and immune-related pathological processes. Immune infiltration analyses further indicate that these genes are closely associated with immune-cell activity in RA. Overall, the study provides new insight into RA pathogenesis and supports the potential clinical relevance of CD83 and CRIP2, although further experimental and clinical validation is required.
Conclusion
This study offers valuable understanding about RA pathogenesis and identifies probable diagnostic biomarkers as well as therapeutic targets (CD83 and CRIP2), which could improve our awareness of the illness and help with formulating more successful care plans.