Altered expression of miR-146a in myasthenia gravis

The purpose of this study was to analyze the expression of miR-146a in PBMCs obtained from patients with myasthenia gravis (MG) and healthy controls and to investigate the effect of the inhibition of miR-146a on the activation of AchR specific B cells obtained from mice. The expression of miR-146a levels in PBMCs obtained from patients with MG and healthy controls were determined by qRT-PCR. MiR-146a's complementary fragment, AntagomiR-146a, was synthesized as inhibitor, and the nonfunctional fragment, which has similar construction to AntagomiR-146a, was synthesized as negative control inhibitor. The expression of miR-146a, CD40, CD80 and CD86 on AchR specific B cells were analyzed by qRT-PCR and flow cytometry. Western blotting was used to detect the expression of TLR4, NF-kappa B and Bcl-2. The expression of miRNA-146a in PBMCs obtained from patients with MG was significantly upregulated compared to healthy controls (P < 0.01). Transfection with miR-146a inhibitor dramatically decreased expression of miR-146a, CD40, CD80, TLR4 and NF-kappa B on AchR specific B cells compared to mock transfected cells. We conclude that abnormal expression/regulation of miR-146a may play an important role in the regulation of AchR specific B cells and contribute to the pathogenesis of MG. (C) 2013 Elsevier Ireland Ltd. All rights reserved.