The online version of this article (doi:10.1186/s13075-017-1492-9) contains supplementary material, which is available to authorized users.
Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from “at-risk” to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from “at-risk” to RA.
We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + “at-risk” individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors.
We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals.
This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker.
Additional file 1: Baseline characteristics of individuals for pilot and validation phases. (DOCX 262 kb)
Additional file 3: Serum miRNAs miR-146a and miR-155 expression levels in the pilot phase. (DOCX 19324 kb)
Additional file 4: List of miRNAs of interest with age adjustment in the validation phase. (DOCX 119 kb)
Additional file 8: Associations between clinical variables and dCt at baseline for key miRNAs. (DOCX 11 kb)
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- Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis
E. M. A. Hensor
J. L. Nam
N. A. Barnes
M. F. McDermott
M. H. Buch
- BioMed Central
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