Stascheit Frauke, Hotter Benjamin, Hoffmann Sarah, Kohler Siegfried, Lehnerer Sophie, Sputtek Andreas, Meisel Andreas
Department of Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
J Transl Autoimmun. 2021 Aug 10;4:100111. doi: 10.1016/j.jtauto.2021.100111. eCollection 2021.
Myasthenia gravis (MG) is the most common autoimmune disease affecting the neuromuscular junction by specific autoantibodies. The etiology of MG and its heterogeneity in clinical courses are poorly understood, although it was recently shown that gut microbial dysbiosis plays a critical role. Since levels of Calprotectin (CLP) seem to correlate with level of dysbiosis, we hypothesize that CLP may serve as potential disease activity biomarker in MG. Sera from 251 patients with MG and 90 controls were analyzed in an explorative, cross-sectional design. Prospectively, we tested CLP levels in MG patients up to 3 years. Association of CLP levels with socio-demographics, disease activity (quantitative myasthenia gravis (QMG) score, myasthenia gravis-specific Activities of Daily Living scale (MG-ADL)), antibody (Abs) status, history of myasthenic crisis, treatment regime, and history of thymectomy were investigated using univariate analysis. Mean baseline serum levels of CLP were significantly higher in MG patients compared to controls (4.3 μg/ml vs. 2.1 μg/ml; < 0.0001). Higher levels of CLP were associated with a higher clinical disease severity measured by MGFA classification and QMG score. Nevertheless, the only weak correlation of CLP with clinical outcome parameters needs confirmation in future studies. Currently, there are no validated blood biomarkers for MG. The significantly elevated CLP and mild correlation with parameters of disease activity suggests that CLP holds promise as a biomarker for measurement of individual disease severity.
重症肌无力(MG)是最常见的一种由特异性自身抗体影响神经肌肉接头的自身免疫性疾病。尽管最近研究表明肠道微生物失调起着关键作用,但MG的病因及其临床病程的异质性仍知之甚少。由于钙卫蛋白(CLP)水平似乎与失调程度相关,我们推测CLP可能作为MG潜在的疾病活动生物标志物。采用探索性横断面设计分析了251例MG患者和90例对照者的血清。前瞻性地,我们检测了MG长达3MG患者长达3年的CLP水平。使用单因素分析研究CLP水平与社会人口统计学、疾病活动(重症肌无力定量评分(QMG)、重症肌无力日常生活活动量表(MG-ADL))、抗体(Abs)状态、重症肌无力危象病史、治疗方案和胸腺切除术史之间的关联。与对照组相比,MG患者的平均基线血清CLP水平显著更高(4.3μg/ml对2.1μg/ml;<0.0001)。较高的CLP水平与MGFA分类和QMG评分所衡量的更高临床疾病严重程度相关。然而,CLP与临床结局参数之间唯一的弱相关性需要在未来研究中得到证实。目前,尚无经过验证的MG血液生物标志物。CLP显著升高且与疾病活动参数存在轻度相关性,这表明CLP有望作为衡量个体疾病严重程度的生物标志物。