Circulating Small Noncoding RNA Biomarkers of Response to Triple Disease-modifying Antirheumatic Drug Therapy in White Women With Early Rheumatoid Arthritis
ObjectiveTo identify small noncoding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA).MethodsEarly RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as European League Against Rheumatism responders or nonresponders. 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 human sncRNA. Differential expression analysis was performed, comparing responders (n = 24) and nonresponders (n = 18).ResultsPretreatment levels of 4 sncRNA were significantly increased in nonresponders: chr1. tRNA131-GlyCCC (4.1-fold, adjusted P = 0.01), chr2.tRNA13-AlaCGC (2.2-fold, adjusted P = 0.02), U2-L166 (6.6-fold, adjusted P = 0.02), and piR-35982 (2.4-fold, adjusted P = 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adjusted P = 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 anticodon loop, consistent with these sncRNA having roles as 5′ translation interfering tRNA halves (tiRNA).ConclusionPretreatment levels of specific serum sncRNA might facilitate identification of patients more likely to respond to triple DMARD therapy.