Background/Purpose:  MicroRNAs (miRNAs) are a group of single-stranded non-coding RNAs of 20-25 nucleotides in length that can potentially regulate every aspect of cellular function. Recent studies have demonstrated that miRNAs can be detected in the circulation and serve as potential biomarkers of various diseases. Our aim was to evaluate whether AS pathogenesis is related to the aberrant expression of plasma miRNAs.

Methods: The expression profile of 800 miRNAs was determined in pooled RNA samples from plasma of AS patients and healthy donors (HDs) (n=3 each) using a nCounter miRNA assay. Next, candidate miRNAs were validated by real time RT-PCR in a validation cohort of 26 AS patients and 26 HDs. To evaluate their relevance in the AS pathogenesis, an analysis was carried out by using the web-based bioinformatics tool IPA. Association studies with the clinical status of the AS patients were also performed. AS activity was defined as BASDAI ≥ 4, CRP > 8 mg/L and ESR > 20 mm/h. Structural damage was evaluated by mSASSS.

Results:  In discovery phase, nine miRNAs were differentially expressed (fold change ≥ 2) in the plasma of AS patients vs. HDs. After validation, seven of the nine miRNAs clearly distinguished AS plasma samples with high confidence level (P < 0.05). Specifically, the circulating levels of miR-146a-5p, miR-125a-5p, and miR22-3p were upregulated, whereas those of miR-320e, miR-151-3p, miR150-5p and miR-451a were downregulated in AS patients vs. HDs. The ROC curve analyses of these miRNAs exhibited a moderate distinguishing efficiency, with the AUCs for these miRNA ranging from 0.674 to 0.746. In addition, target gene prediction by IPA analysis showed that these altered miRNAs were involved in affecting various aspect of AS, such as signaling pathways related to inflammatory response and bone turnover. Association studies showed that plasma miR-146a-5p expression was significantly increased in active AS patients as compared with non-active AS patients (P = 0.037). In addition, we observed that AS patients with higher structural damage exhibited significantly lower miR-151-3p expression than those with less radiographic severity (P = 0.045); the ROC curve analyses showed that relative expression of this miRNA could distinguish AS patients with radiographic severity, with a power AUC of 0.761 (P= 0.05).

Conclusion:  This study has identified a set of circulating miRNAs which could be attractive candidates as noninvasive biomarkers for the diagnosis of AS patients and may help elucidate the pathogenesis of AS. Funded by PI-0314-2012, SER

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-microrna-expression-profiles-in-ankylosing-spondylitis-patients/