The decipherment of tissue-based proteome signatures revealed predictive biomarkers of diseases for primary Sjogren's syndrome with peripheral neuropathy system

Abstract Background and objectives The peripheral neuropathy system in Primary Sjogren's syndrome (pSS-PNS) is often disregarded as a significant neuropathy, and there is limited research on the underlying pathological mechanisms. This study aimed to explore some possible processes by proteomic analysis. Methods Samples of the sural nerve were collected from patients diagnosed with pSS-PNS (n=3) and chronic inflammatory demyelinating polyneuropathy (CIDP) (control, n=3). A data-independent acquisition (DIA) proteomic analysis was used to detect differentially expressed proteins (DEPs). Functional annotation of DEPs and gene modules was performed using Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), Protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The targeted proteins were validated using the parallel reaction monitoring (PRM) method. Results Samples of the sural nerve were collected from pSS-PNS patients (n=3) and CIDP patients (n=3)，and subjected to differential proteomic analysis (DIA). As a result, 187 proteins were found to be significantly regulated between pSS-PNS patients and the control group. 42 of these proteins were selected for quantification through parallel reaction monitoring (PRM), and five of them (F2, FGG, FN1, INA, FERMT3) displayed consistent expression patterns between DIA and PRM. Conclusion F2, FGG, FN1, INA, and FERMT3 exhibited differential expression in the sural nerves of patients with PNS secondary to Sjögren's syndrome (pSS-PNS). These genes have the potential to serve as diagnostic and therapeutic targets for pSS-PNS, and their pathogenesis may be linked to platelet activation.