tRF-21-LNK8KEP1B as a potential novel diagnostic biomarker for enthesitis-related arthritis

Objective: tRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, and widely distribute in human tissues, including blood and urine. The diagnosis of enthesitis-related arthritis (ERA) is based on the observation of clinical manifestations. Therefore, we aimed to investigate whether serum tRFs can be used as diagnostic markers for ERA. Methods: Serum was collected from children admitted to the Children's Hospital Affiliated with Nanjing Medical University between February 2022 to October 2022. The expression profiles of tRFs in the serum of ERA patients (n = 5) and healthy controls (HCs; n = 5) were investigated using small RNA high-throughput sequencing. The level and diagnostic value of tRF-21-LNK8KEP1B were evaluated by real-time quantitative PCR in serum samples from 30 ERA patients and 31 HCs. The specificity and sensitivity of tRFs were determined using receiver operating characteristic analyses. Bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs. Results: Ninety-eight upregulated and 63 downregulated tRFs were identified in the serum. We selected tRF-21LNK8KEP1B as a candidate marker using KEGG pathway enrichment and PCR validation. tRF-21-LNK8KEP1B was substantially increased in the serum of ERA patients compared with that in HCs. The area under the curve (AUC) for tRF-21-LNK8KEP1B in the ERA group was 0.7849. Conclusions: Collectively, we demonstrated the promising role of serum tRF-21-LNK8KEP1B-levels as a diagnostic biomarker for ERA.