重症肌无力(MG)的循环microRNA

A. Punga, T. Punga
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摘要

预测重症肌无力(MG)临床病程的主要困难之一是疾病的异质性,根据患者的亚组,疾病进展差异很大。MG亚组按发病年龄划分[早发性MG (EOMG;发病≤50年)与晚发性MG (long;发病[50年];存在胸腺瘤(胸腺瘤相关MG),抗体亚型[乙酰胆碱受体抗体血清阳性(AChR+),肌肉特异性酪氨酸激酶抗体血清阳性(MuSK+)],或存在针对低密度脂蛋白受体相关蛋白4 (Lrp4)或agrin的抗体以及临床亚型(眼部与全身MG)。MG的诊断试验,如抗体滴度、神经生理试验和客观临床疲劳评分,并不一定反映疾病进展。因此,非常需要可靠、客观的MG生物标志物来跟踪疾病进程和个体化治疗对个体化药物的反应。在这方面,循环microRNAs (miRNAs)已成为有希望的潜在生物标志物,因为它们在体液中的可及性和在不同疾病(包括自身免疫性疾病)中的独特特征。几项关于MG亚型循环miRNA的研究揭示了患者血清中的特异性miRNA谱。在全身性AChR+ EOMG中,miR-150-5p和miR-21-5p是升高最多的mirna,在免疫抑制和胸腺切除术治疗后观察到较低的水平。在AChR+广泛性LOMG中,miR-150-5p、miR-21-5p和miR-30e-5p水平在免疫抑制后的临床反应中升高或降低。在眼部MG中,较高水平的miR-30e-5p将患者与其他眼部MG区分开来。相反,在MuSK+ MG中,let-7 miRNA家族成员的水平升高。关于Lrp4或agrin抗体血清阳性MG的循环miRNA谱的研究仍然缺乏。本文综述了目前对MG不同亚组循环mirna的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating microRNA in Myasthenia gravis (MG)
One of the main difficulties in predicting the clinical course of Myasthenia Gravis (MG) is the heterogeneity of the disease, where disease progression differs greatly depending on the patient's subgroup. MG subgroups are classified according to the age of onset [early onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset >50 years]; the presence of a thymoma (thymoma associated MG), antibody subtype [acetylcholine receptor antibody seropositive (AChR+), muscle-specific tyrosine kinase antibody seropositive (MuSK+)], or presence of antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4) or agrin as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue scores, do not necessarily reflect disease progression. Hence, there is a great need for reliable, objective biomarkers in MG to follow the disease course and the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patient sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decreased by the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.
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