Serum exosome smallRNA array analysis identifies 5'tiRNA-PheGAA and tRF-1-IleAAT as potential biomarkers for diagnosis of rheumatoid arthritis.

tRNA-derived small RNAs (tsRNAs) are a recently identified class of non-coding RNAs (ncRNAs) that exhibit aberrant expression in various diseases and are involved in multiple pathological processes. In this study, we isolated exosomes from the serum of patients with rheumatoid arthritis (RA) and healthy individuals, and extracted total RNA for analysis using small RNA microarrays and tsRNA sequencing. We identified 866 tsRNAs that were differentially expressed between RA patients and healthy controls, with 146 upregulated and 720 downregulated. Among the upregulated tsRNAs, the five with the most significant increases were selected for further validation. qRT-PCR analysis confirmed that 5'tiRNA-PheGAA and tRF-1-IleAAT were significantly upregulated in RA patients. Pathway enrichment analysis suggested that these two tsRNAs are involved in tryptophan metabolism, autophagy, chemokine signaling, Rap1 signaling, and focal adhesion pathways. ROC curve analysis indicated that both tsRNAs exhibit strong diagnostic potential for RA. Collectively, our findings demonstrate that serum exosomal tsRNAs may serve as promising biomarkers for the effective diagnosis and prognosis of rheumatoid arthritis.