Circulating Small Non-Coding RNA Biomarkers of Response to Triple DMARD Therapy in Caucasian Women With Early Rheumatoid Arthritis

J Rheumatol. 2020 Jun 15;jrheum.191012. doi: 10.3899/jrheum.191012. Online ahead of print.


Objective: To identify small non-coding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA).

Methods: Early RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate + sulphasalazine + hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as EULAR responders or non-responders. RNA was isolated from 42 archived serum samples, collected prior to commencement of triple DMARD therapy. Small RNA sequencing was performed and the reads mapped to annotations in a database of small human non-coding RNAs. Differential expression analysis was performed, comparing responders (n=24) and non-responders (n=18).

Results: Pre-treatment levels of 4 sncRNAs were significantly increased in non-responders: chr1.tRNA131-GlyCCC (4.1-fold, adj.P-value: 0.01); chr2.tRNA13-AlaCGC (2.2-fold, adj.Pvalue: 0.02); U2-L166 (6.6-fold, adj.P-value: 0.02); and piR-35982 (2.4-fold; adj.P-value: 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adj.Pvalue: 0.01). Reads for chr1.tRNA131-GlyCCC and chr2.tRNA13-AlaCGC mapped to the 5' end of each tRNA gene and were truncated at the anti-codon loop, consistent with these sncRNAs having roles as 5' translation interfering tRNA halves (tiRNAs).

Conclusion: Pre-treatment levels of specific serum sncRNAs might facilitate identification of patients more likely to respond to triple DMARD therapy.