Background microRNA (miRNA) expression pattern is believed to be reflective of underlying pathophysiologic processes and is specific to various disease states. At present there are no studies that have established a miRNA based signature profile in patients with axial Spondyloarthritis (SpA). We hypothesized that patients with axial SpA have aberrantly expressed circulating miRNAs reflective of underlying disease and inflammation and these dysregulated miRNAs can be detected through miRNA expression profiling.
Objectives To determine the expression profile of miRNAs in plasma of patients with axial SpA and compare it with healthy, age and sex-matched controls.
Methods 15 subjects with axial SpA based on the Assessment of Spondyloarthritis International Society (ASAS) classification criteria and 5 controls were recruited from our registry. Demographic data were collected and disease activity was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Peripheral blood samples (5 ml) were obtained from eligible consenting patients and controls. RNA from the plasma was prepared using miRNeasy kit (Qiagen) by a modified protocol. Expression of 175 miRNAs was screened in the plasma of all 15 patients and 5 controls using serum/plasma miRNA PCR arrays (Exiqon Inc. Woburn, MA) essentially following the manufacturer’s instructions. Real-time PCR was carried out on StepOne Plus (Applied Biosystems) and the data was extracted and analyzed using ExiGen Enterprise software (MultiD, GöteborgSweden). Potential miRNA gene targets were identified using bioinformatics. Comparison between patients and controls was performed using 2 sample t Test. ESR and CRP levels were measured using standard laboratory methods.
Results Of 19 patients; 60% were males, median age of 52 years (range 22-66) with mean BASDAI of 5.24. Mean level of ESR was 16.94 mm/hr and CRP was 0.74 mg/dl. 7 differentially expressed miRNAs (2 upregulated and 5 downregulated) (Table-1) were identified in plasma of patients SpA. miR-34a, associated with bone morphogenesus and growth was overexpressed and was predicted to target BMP-3 mRNA by TargetscanS and PicTar miRNA target algorithms. miR-150 was downregulated in all of the patient samples analyzed using the TaqMan Gene Expression assay. The most repressed miRNA was miR-16 and is predicted to regulate the expression of Activin A receptor (ACVR2B)-a receptor for growth and differentiation factor-5 (GDF-5). These dysregulated miRNAs may be contributing to the pathogenesis of SpA.
Conclusions Patients with axial SpA, as compared to controls, have dysregulated expression of selected miRNAs in the plasma; and the differentially expressed miRNAs are predicted to target genes that play a role in bone morphogenesis, growth and immune response.
Disclosure of Interest None Declared
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