Bhandage Amol K, Kenina Viktorija, Huang Yu-Fang, Roddate Marija, Kauke Gundega, Grosmane Arta, Žukova Violeta, Eriksson Niclas, Gabrysch Katja, Punga Tanel, Punga Anna Rostedt
Department of Medical Sciences, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
Department of Neurology, Paul Stradinš Clinical University Hospital, Riga, Latvia.
iScience. 2024 Jul 23;27(8):110564. doi: 10.1016/j.isci.2024.110564. eCollection 2024 Aug 16.
There is an unmet need for objective disease-specific biomarkers in the heterogeneous autoimmune neuromuscular disorder myasthenia gravis (MG). This cross-sectional study identified a signature of 23 inflammatory serum proteins with proximity extension assay (PEA) that distinguishes acetylcholine receptor antibody seropositive (AChR+) MG patients from healthy controls (HCs). CCL28, TNFSF14, 4E-BP1, transforming growth factor alpha (TGF-α), and ST1A1 ranked top biomarkers. TGF-β1 and osteoprotegerin (OPG) differed between early- and late-onset MG, whereas CXCL10, TNFSF14, CCL11, interleukin-17C (IL-17C), and TGF-α differed significantly with immunosuppressive treatment. MG patients with moderate to high disease severity had lower uPA. Previously defined MG-associated microRNAs, miR-150-5p, miR-30e-5p, and miR-21-5p, correlated inversely with ST1A1 and TNFSF14. The presented inflammatory proteins that distinguish AChR+ MG are promising serum biomarkers for validation in prospective studies to allow for molecular signatures for patient subgroup stratification and monitoring of treatment response.
在异质性自身免疫性神经肌肉疾病重症肌无力（MG）中，对于客观的疾病特异性生物标志物存在未满足的需求。这项横断面研究通过邻近延伸分析（PEA）确定了23种炎症血清蛋白的特征，该特征可区分乙酰胆碱受体抗体血清阳性（AChR+）的MG患者与健康对照（HCs）。CCL28、TNFSF14、4E-BP1、转化生长因子α（TGF-α）和ST1A1位列顶级生物标志物。TGF-β1和骨保护素（OPG）在早发型和晚发型MG之间存在差异，而CXCL10、TNFSF14、CCL11、白细胞介素-17C（IL-17C）和TGF-α在免疫抑制治疗后有显著差异。疾病严重程度为中度至高度的MG患者uPA较低。先前定义的与MG相关的微小RNA，即miR-150-5p、miR-30e-5p和miR-21-5p，与ST1A1和TNFSF14呈负相关。所呈现的可区分AChR+ MG的炎症蛋白有望成为血清生物标志物，以便在前瞻性研究中进行验证，从而为患者亚组分层和治疗反应监测提供分子特征。
