A Distinct Immunological Signature in Late-Onset Myasthenia Gravis: Insights from an Exploratory Proteomics Study.

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-09-06 DOI:10.1002/ana.78017

Bhaskar Roy, Jiaxin Chen, Fatemeh Khani-Habibabadi, Nilay McLaren, Betty C Soliven, Vern C Juel, Kevin C O'Connor, Richard J Nowak, Linda L Kusner, Henry J Kaminski

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引用次数: 0

Abstract

Objective: Approximately 80% of patients with myasthenia gravis (MG) have autoantibodies against acetylcholine receptor, and clinical characteristics may vary between early-onset (symptom onset age <50 years) and late-onset MG (EOMG and LOMG), but the pathophysiological differences between EOMG and LOMG are not well established.

Methods: We performed an exploratory in-depth proteomics analysis examining 768 inflammatory proteins utilizing the baseline serum samples from the BeatMG study (NCT02110706). We performed pathway enrichment analysis to assess the pathways involved in LOMG. A total of 15 selected proteins from the initial analysis were further examined using the UK Biobank and further quantified in a separate validation cohort.

Results: A total of 21 patients with EOMG (age 38.3 ± 12.1 years, 16 women [76.2%]) and 28 patients with LOMG (age 67.3 ± 8.6 years, 7 women [25%]) from the BeatMG study were included in the exploratory analysis. Several proteins involved in the regulation of leukocyte differentiation and myeloid leukocyte differentiation and migration pathways were more abundant in the LOMG group. Among them, 7 were significantly different in the UK Biobank cohort. A total of 80 participants (39 MG patients (age 54.33 ± 18.9 years, 17 women [43.6%]) and 41 healthy controls (age 49.56 ± 17.06 years, 21 women [66.1%]) were included in the validation cohort, and IL18R1, CXCL17, and CCL11 were validated to be specific for LOMG.

Interpretation: Growing evidence supports that LOMG has a distinct immune pathomechanism. Further prospective studies are warranted to confirm the utility of these proteins as biomarkers of LOMG, and the feasibility of using them for more precise therapeutic targets to improve patient outcomes. ANN NEUROL 2025.

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迟发性重症肌无力的独特免疫学特征：一项探索性蛋白质组学研究的见解。

目的：大约80%的重症肌无力（MG）患者有针对乙酰胆碱受体的自身抗体，其临床特征可能因早发（症状发作）年龄而异。方法：我们进行了探索性的深入蛋白质组学分析，利用BeatMG研究（NCT02110706）的基线血清样本检测了768种炎症蛋白。我们通过途径富集分析来评估LOMG中涉及的途径。从初始分析中选择的15种蛋白质使用UK Biobank进一步检查，并在单独的验证队列中进一步量化。结果：BeatMG研究共纳入21例EOMG患者（年龄38.3±12.1岁，女性16例[76.2%]）和28例LOMG患者（年龄67.3±8.6岁，女性7例[25%]）进行探索性分析。在LOMG组中，参与调节白细胞分化和髓系白细胞分化和迁移途径的几种蛋白质更为丰富。其中，7个在UK Biobank队列中存在显著差异。验证队列共纳入80名参与者(39名MG患者（年龄54.33±18.9岁，17名女性[43.6%]）和41名健康对照（年龄49.56±17.06岁，21名女性[66.1%]），并验证IL18R1、CXCL17和CCL11对LOMG具有特异性。解释：越来越多的证据支持long具有独特的免疫病理机制。需要进一步的前瞻性研究来证实这些蛋白作为LOMG生物标志物的效用，以及使用它们作为更精确的治疗靶点以改善患者预后的可行性。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.