Identification of Serum miR-146a and miR-155 as Novel Noninvasive Complementary Biomarkers for Ankylosing Spondylitis

Study Design. Prospective serum microRNAs study. Objective. To investigate differentially expressed serum microRNAs (miRNAs) between ankylosing spondylitis (AS) patients and controls, and to evaluate the potential of miRNAs as biomarkers for AS. Summary of Background Data. There is an urgent need to explore novel biomarkers with more high sensitivity and specificity for the diagnosis of AS, especially for early-stage AS. Recently, the discovery of miRNAs has paved a new avenue for the diagnosis of cancers and other diseases, However, the global serum miRNAs pattern in AS patients has never been determined. Methods. An initial screening of miRNA expression by Solexa sequencing was performed using serum samples pooled from 10 AS patients and 10 controls, respectively. Subsequently, differential expression was validated using hydrolysis probe-based stem loop quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, AS patients were divided into group A (kyphosis <70 degrees) and group B (kyphosis >= 70 degrees). Disease activity and functional status were evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASH), respectively. The areas under the receiver-operating characteristic (ROC) curves of identified miRNAs were analyzed. Results. Nineteen serum miRNAs were differentially expressed in AS patients compared with controls. After qRT-PCR confirmation, miR-146a and miR-155 were significantly upregulated in AS patients. The areas under the ROC curves using miR-146a and miR-155 were 0.917 and 0.964, respectively. Importantly, the miR-155 expression level in group B was significantly higher than that in group A. In addition, significant correlation was observed between miR-155 expression level and BASDAI (r = 0.5, P < 0.01). Conclusion. Detection of serum miRNAs (rniR-146a and miR-155) may serve as novel complementary biomarkers for AS. Moreover, the expression level of miR-155 is suggested to be associated with disease activity and the severity of thoracolumbar kyphosis secondary to AS.