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通过质谱法鉴定视神经脊髓炎谱系障碍中与髓鞘形成和胆固醇转运相关的新型血清蛋白

Identification of Novel Serum Proteins Associated with Myelination and Cholesterol Transport in Neuromyelitis Optica Spectrum Disorders by Mass Spectrometry.

作者信息

John Mathew, Maria Evelyn, Das Sonu, T Harisuthan

机构信息

Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala India.

Department of Neurology, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala India.

出版信息

Indian J Clin Biochem. 2022 Jul;37(3):275-284. doi: 10.1007/s12291-021-01004-w. Epub 2021 Nov 12.

Abstract

UNLABELLED

Neuromyelitis optica spectrum disorders (NMOSD) is a demyelinating autoimmune disease affecting the central nervous system causing inflammatory lesions in the optic nerves, spinal cord and other vital areas of CNS. The clinical manifestations include acute transverse myelitis with paraplegia and optic neuritis with impaired vision. In the present study we focussed on comparative expression of serum proteins between NMOSD variants and control. The study has identified a plethora of novel and unexplored acute phase proteins involved in lipid transport and myelination in perspective of NMOSD. The serum proteins obtained after albumin globulin depletion were subjected to LC-MS/MS. The commonly altered proteins in all NMOSD variants with respect to control were smaug homolog protein and serum amyloid A. Truncated breast and ovarian cancer susceptibility protein and cystic fibrosis transmembrane conductance regulator protein were specifically upregulated and can act as potential biomarkers for neuromyelitis optica with autoantibody negativity to Aquaporin - 4 (AQP-4) and myelin oligodendrocyte (MOG) immunoglobulins. In addition, the uniquely downregulated proteins such as antithrombin III and histidine rich glycoprotein in NMO/MOG autoantibody negative samples can be accounted for its dysregulated fibrinolysis associated with NMO. The differentially expressed proteins were involved in cholesterol transport, synaptic vesicle mediated transport, neurotransmission and immune regulation which are closely associated with myelin formation and protection

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12291-021-01004-w.

摘要

未标记

视神经脊髓炎谱系障碍(NMOSD)是一种影响中枢神经系统的脱髓鞘自身免疫性疾病,会在视神经、脊髓和中枢神经系统的其他重要区域引起炎症性病变。临床表现包括伴有截瘫的急性横贯性脊髓炎和伴有视力受损的视神经炎。在本研究中,我们聚焦于NMOSD变体与对照组之间血清蛋白的比较表达。该研究从NMOSD的角度鉴定出了大量参与脂质转运和髓鞘形成的新型且未被探索的急性期蛋白。白蛋白球蛋白耗尽后获得的血清蛋白进行了液相色谱-串联质谱分析。与对照组相比,所有NMOSD变体中常见的蛋白变化是Smaug同源蛋白和血清淀粉样蛋白A。截短的乳腺癌和卵巢癌易感蛋白以及囊性纤维化跨膜传导调节蛋白被特异性上调,可作为针对水通道蛋白-4(AQP-4)和髓鞘少突胶质细胞(MOG)免疫球蛋白自身抗体阴性的视神经脊髓炎的潜在生物标志物。此外,在NMO/MOG自身抗体阴性样本中独特下调的蛋白,如抗凝血酶III和富含组氨酸的糖蛋白,可归因于与NMO相关的纤维蛋白溶解失调。差异表达的蛋白参与胆固醇转运、突触小泡介导的转运、神经传递和免疫调节,这些与髓鞘形成和保护密切相关。

补充信息

在线版本包含可在10.1007/s12291-021-01004-w获取的补充材料。

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