Identification of shared diagnostic biomarkers and potential co-morbidity mechanisms between primary Sjogren's syndrome and chronic kidney disease.

Abstract

Background: The mechanisms linking primary Sjogren's syndrome (pSS) to chronic kidney disease (CKD) are obscure. Our study sought to uncover shared genetic connections and pathways between these conditions.

Methods: Datasets for pSS and CKD were sourced from GEO. WGCNA alongside differential expression assessment was employed to pinpoint common genes. GO and KEGG were applied for gene enrichment. Key genes were selected using LASSO, Random Forest, and SVM-RFE. Clinical prediction models were constructed using multi-factor logistic regression. GSEA and immune infiltration analyses explored the mechanisms linking key genes in pSS and CKD. MR analysis and SMR approach assessed the genetic link between pSS and CKD, evaluating the impact of co-shared genes on these conditions.

Result: We identified 104 common genes using WGCNA and differential expression analysis. GO and KEGG analyses hinted at cancer involvement in both diseases. Machine learning models pinpointed five genes as strong diagnostic biomarkers for both pSS and CKD, with NUDT1 and COMMD2 validated in independent cohorts. Clinical prediction models were constructed based on these two genes. GSEA and immune infiltration analysis suggested immune processes, particularly T cell infiltration, were implicated in both diseases. Bidirectional MR analysis failed to establish a causal link between the two diseases, yet SMR analysis revealed associations between NUDT1 and COMMD2 expression and the development of pSS and CKD.

Conclusion: This study uncovered crucial genes shared between pSS and CKD, shedding light on their co-morbidity mechanisms and possible diagnostic biomarkers. Key Points • This study unveils for the first time the immunological association between PSS and CKD. • NUDT1 and COMMD2 are identified as key molecules in the comorbidity mechanism of PSS and CKD. • A diagnostic model for the comorbidity of PSS and CKD is constructed.