Department of Neurology, the Second Affiliated Hospital of Guangzhou Medical University, 250# Changgang east Road, Guangzhou, Guangdong 510260, China; RayBiotech, Inc., Guangzhou, 79 Ruihe Road, Huangpu District, Guangzhou, Guangdong, China; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China; South China Biochip Research Center, Guangzhou 510630, China.
Department of Neurology, the Second Affiliated Hospital of Guangzhou Medical University, 250# Changgang east Road, Guangzhou, Guangdong 510260, China; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
Mult Scler Relat Disord. 2022 Mar;59:103527. doi: 10.1016/j.msard.2022.103527. Epub 2022 Jan 20.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory demyelinating disorder of the central nervous system (CNS), which mainly affects the optic nerves and spinal cord. The aims of this study were to determine whether the expression levels of serological cytokines could distinguish 1) NMOSD from healthy controls (HCs); and 2) NMOSD patients with and without the aquaporin-4 (AQP4) antibody biomarker from each other; and 3) NMOSD patients without the antibody to AQP4 from MS patients.
The expression levels of 200 proteins in serum from 41 NMOSD (32 with antibodies to AQP4, 9 without antibodies to AQP4), 12 MS patients, and 34 HCs were measured using glass-based antibody arrays. None of the patients received any immunosuppressive treatment. In parallel, the correlation between protein expression in NMOSD/MS patients and clinical traits was determined with Weighted Gene Co-expression Network Analysis (WGCNA).
Thirty-nine serological proteins were differentially expressed in NMOSD patients compared to HCs, with 29 of these proteins not observed in MS patients. In addition, the data reveal 15 differentially-expression proteins (DEPs) between AQP4-IgG seronegative and AQP4-IgG seropositive NMOSD patients, and 9 DEPs between NMOSD and MS patients who did not have AQP4-IgG.
Serological IL-17B is significantly upregulated in both NMOSD and MS patients compared to HCs, and could be a key biomarker of NMOSD and MS. Serological VEGF, MPIF-1 and NrCAM were positively associated with AQP4-IgG titer. We also demonstrate that EGF may be involved in the breakdown of the BBB by downregulating Claudin-5.
视神经脊髓炎谱系疾病（NMOSD）是一种罕见且严重的中枢神经系统（CNS）炎症性脱髓鞘疾病，主要影响视神经和脊髓。本研究旨在确定血清细胞因子的表达水平是否可以区分：1）NMOSD 与健康对照（HCs）；2）NMOSD 患者与各自的水通道蛋白-4（AQP4）抗体生物标志物；3）NMOSD 患者与多发性硬化症（MS）患者。
使用玻璃基抗体阵列测量了 41 名 NMOSD 患者（32 名抗 AQP4 抗体阳性，9 名抗 AQP4 抗体阴性）、12 名 MS 患者和 34 名 HCs 的血清中 200 种蛋白质的表达水平。所有患者均未接受任何免疫抑制治疗。同时，使用加权基因共表达网络分析（WGCNA）确定 NMOSD/MS 患者的蛋白表达与临床特征之间的相关性。
与 HCs 相比，NMOSD 患者有 39 种血清蛋白表达差异，其中 29 种蛋白未在 MS 患者中观察到。此外，数据显示，AQP4-IgG 阴性和 AQP4-IgG 阳性 NMOSD 患者之间有 15 个差异表达蛋白（DEPs），NMOSD 和 MS 患者之间没有 AQP4-IgG 的有 9 个 DEPs。
与 HCs 相比，NMOSD 和 MS 患者的血清白细胞介素-17B（IL-17B）显著上调，可能是 NMOSD 和 MS 的关键生物标志物。血清血管内皮生长因子（VEGF）、单核细胞趋化蛋白 1（MPIF-1）和神经细胞黏附分子（NrCAM）与 AQP4-IgG 滴度呈正相关。我们还表明，EGF 可能通过下调紧密连接蛋白-5 参与 BBB 的破坏。
