Background Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammatory back pain and enthesis. MicroRNA (miRNA) are an abundant class of small RNA that can play an important role in gene regulation and participate in many physiological and pathological process^[1]. According to the microarray results previously, our group found that the expression levels of miR-17–5p, miR-27a, miR-29a and miR-126–3p were higher in AS group than in healthy group. Moreover, the expression levels of miR-17–5p downregulated significantly after regular etanercept treatment, while the other 3 microRNAs slightly upregulated. Another study also reported elevated miR-29a expression in PBMCs of patients with AS^[3], while no further study on investigating the treatment effect on miRNA expression.

Objectives To investigate the expression level of the four miRNAs mentioned before in AS and healthy controls. The changes of microRNAs expressions after regular therapies are also the focus of our study.

Methods We initially validated the expression levels of miR-17–5p, miR-27a, miR-29a, miR-126–3p in the PBMCs of AS (n=99) and healthy controls (n=39) using real-time quantitative reverse transcription PCR (qRT-PCR). Patients with AS were divided into 4 groups according to their different therapies, including 12-week Celecoxib/Etanercept /combination therapy and 24-week rh TNFR:Fc therapy (n=16, n=23, n=22 and n=38 respectively). Fold change for each reaction was calculated as 2 − ΔΔCt.

Results Significantly higher expression of the four miRNAs (miR-17–5p, miR-27a, miR-29a and miR-126–3p) were observed in AS (ΔCt value: 4.40±2.02, 6.75±1.58, 1.52±1.12 and 2.34±1.58, p<0.001, respectively) than in healthy controls (ΔCt value: 6.15±1.41, 8.05±0.86, 4.29±1.16, and 4.17±1.01, p<0.001, respectively). The corresponding fold changes were 3.34 (0.61–18.37), 2.47 (0.71–8.59), 6.82 (2.24–20.79) and 3.55 (0.96–13.06). Moreover, expressions of miRNAs were dramatically downregulated after 24-week etanercept therapy except miR-29a (p=0.013, p=0.043, p=0.025 and p=0.262 respectively). A 12-week celebrax therapy or combination therapy can significantly reduce the expression level of miR-126–3p (p=0.006 and p=0.016). There were no significant difference between AS patients before and after treatment in miR-17–5p, miR-27a as well as miR-29a.

Conclusions We validated the 4 elevated miRNAs expression in PBMCs of patients with ankylosing spondylitis. Different treatments can reduce the expression of microRNAs to some extent.

1. Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ. Biological functions of microRNAs: a review[J]. Journal of physiology and biochemistry. 2011,67(1):129–39.

2. Lv Q, Li Q, Zhang P, Jiang Y, Wang X, Wei Q, et al. Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets[J]. BioMed research international. 2015,2015:504208.

3. Huang J, Song G, Yin Z, Luo X, Ye Z. Elevated miR-29a expression is not correlated with disease activity index in PBMCs of patients with ankylosing spondylitis[J]. Modern rheumatology/the Japan Rheumatism Association. 2014,24(2):331–4.

Acknowledgement This study was supported by The National Natural Science Foundation of China.

Disclosure of Interest X. Li Grant/research support from: The National Natural Science Foundation of China, Q. Li Grant/research support from: The National Natural Science Foundation of China, J. Gu Grant/research support from: The National Natural Science Foundation of China