Circulating small non-coding RNA biomarkers of response to triple DMARD therapy in Caucasian women with early rheumatoid arthritis

Foers, AD; Garnham, AL; Smyth, GK; Proudman, SM; Cheng, L; Hill, AF; Pang, KC; Wicks, IP

Author(s): Foers, AD; Garnham, AL; Smyth, GK; Proudman, SM; Cheng, L; Hill, AF; Pang, KC; Wicks, IP;
Details: Publication Year 2020-12-01,Volume 47,Issue #12,Page 1746-1751
Journal Title: Journal of Rheumatology
Abstract: 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.
Publisher: Journal of Rheumatology
Keywords: biomarke,rDMARD,rheumatoid arthritis,small noncoding RNA,translation interfering tRNA halves
Research Division(s): Inflammation; Bioinformatics
PubMed ID: 32541082
Publisher's Version: https://doi.org/10.3899/jrheum.191012
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Foers AD et al_J Rheumatology_2020_author manuscript.pdf - (0.54MB, application/pdf)

Creation Date: 2020-06-22 11:52:53

Last Modified: 2021-06-22 10:03:50