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对视神经脊髓炎谱系障碍(NMOSD)和髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)患者血清进行的差异蛋白质组学分析揭示了共同和不同的疾病机制。

A Differential Proteomic Analysis on Patient Sera with Neuromyelitis Spectrum Disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Suggested Shared and Distinct Disease Mechanisms.

作者信息

Hu Xuhan, Sun Xiaobo, Yang Tingting, Sun Xiaoou, Wen Meiling, Chen Changming, Qiu Wei, Jin Ya

机构信息

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

Department of Neurology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

出版信息

J Proteome Res. 2025 Jul 4;24(7):3697-3714. doi: 10.1021/acs.jproteome.5c00382. Epub 2025 Jun 4.

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are two types of autoimmune-mediated central nervous system (CNS) inflammatory demyelinating diseases that have similar clinical manifestations but with different pathogenesis and prognosis. Here, we reported on a differential proteomic analysis on the patient sera with the two diseases. Serum samples of 25 aquaporin-4 (AQP4)-IgG+ NMOSD patients, 16 MOGAD patients, and 8 healthy individuals were submitted to shotgun analysis using nano-LC-MS/MS. Totally, 584 nonredundant proteins were identified and quantified, among which 340 proteins were detected in at least three samples per group. Statistical analysis revealed 40 proteins had significant difference in at least one group-pair comparison (fold change >1.2 or <0.83 and multiple-sample test ANOVA-q < 0.05). Also, 38 proteins were detected only in the patient groups and not in the healthy controls. Bioinformatic analysis on these 78 proteins revealed that disturbance of the immune system, hemostasis processes, and carbohydrate metabolism occurred in both diseases, while the dysregulation patterns suggested different mechanisms. We expect this work would provide useful information to improve the understanding of the mechanisms of NMOSD and MOGAD and suggest potential diagnostic markers and treatment targets.

摘要

视神经脊髓炎谱系障碍(NMOSD)和髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)是两种自身免疫介导的中枢神经系统(CNS)炎性脱髓鞘疾病,它们具有相似的临床表现,但发病机制和预后不同。在此,我们报告了对这两种疾病患者血清的差异蛋白质组学分析。将25例水通道蛋白4(AQP4)-IgG阳性的NMOSD患者、16例MOGAD患者和8名健康个体的血清样本进行纳升级液相色谱-串联质谱(nano-LC-MS/MS)鸟枪法分析。总共鉴定并定量了584种非冗余蛋白质,其中每组至少在三个样本中检测到340种蛋白质。统计分析显示,40种蛋白质在至少一组配对比较中有显著差异(倍数变化>1.2或<0.83,多样本检验方差分析q<0.05)。此外,仅在患者组中检测到38种蛋白质,而在健康对照中未检测到。对这78种蛋白质的生物信息学分析表明,两种疾病均发生免疫系统、止血过程和碳水化合物代谢紊乱,但其失调模式提示了不同的机制。我们期望这项工作将为增进对NMOSD和MOGAD发病机制的理解提供有用信息,并提示潜在的诊断标志物和治疗靶点。

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