Miyachi Yukino, Fujii Takayuki, Yamasaki Ryo, Tsuchimoto Daisuke, Iinuma Kyoko, Sakoda Ayako, Fukumoto Shoko, Matsushita Takuya, Masaki Katsuhisa, Isobe Noriko, Nakabeppu Yusaku, Kira Jun-Ichi
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Front Neurol. 2021 Aug 5;12:681980. doi: 10.3389/fneur.2021.681980. eCollection 2021.
Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical courses and disease severities, it is important to identify biomarkers that predict disease activity and severity. In this study, we assessed the frequencies of serum autoantibodies against mature oligodendrocytes in MS patients using a tissue-based immunofluorescence assay (IFA) to determine whether anti-oligodendrocyte antibodies are associated with the clinical features of MS patients and whether they might be a biomarker to assess CNS tissue damage in MS patients. We assessed the binding of serum autoantibodies to mouse oligodendrocytes expressing Nogo-A, a reliable mature oligodendrocyte marker, by IFA with mouse brain and sera from 147 MS patients, comprising 103 relapsing-remitting MS (RRMS), 22 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS) patients, 38 neuromyelitis optica spectrum disorder (NMOSD) patients, 23 other inflammatory neurological disorder (OIND) patients, and 39 healthy controls (HCs). Western blotting (WB) was performed using extracted mouse cerebellum proteins and IgG from anti-oligodendrocyte antibody-positive MS patients. Tissue-based IFA showed that anti-oligodendrocyte antibodies were positive in 3/22 (13.6%) PPMS and 1/22 (4.5%) SPMS patients but not in RRMS, NMOSD, and OIND patients or HCs. WB demonstrated the target CNS proteins recognized by serum anti-oligodendrocyte antibodies were approximately 110 kDa and/or 150 kDa. Compared with anti-oligodendrocyte antibody-negative MS patients, MS patients with anti-oligodendrocyte antibodies were significantly older at the time of serum sampling, scored significantly higher on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and had a higher frequency of mental disturbance. Although the clinical significance of anti-oligodendrocyte antibodies is still unclear because of their low frequency, anti-oligodendrocyte autoantibodies are potential biomarkers for monitoring the disease pathology and progression in MS.
多发性硬化症（MS）是中枢神经系统（CNS）最常见的炎性疾病，其特征是髓鞘和少突胶质细胞受损。由于MS患者的临床病程和疾病严重程度各不相同，因此识别预测疾病活动和严重程度的生物标志物非常重要。在本研究中，我们使用基于组织的免疫荧光测定法（IFA）评估了MS患者血清中针对成熟少突胶质细胞的自身抗体频率，以确定抗少突胶质细胞抗体是否与MS患者的临床特征相关，以及它们是否可能是评估MS患者中枢神经系统组织损伤的生物标志物。我们通过IFA，利用小鼠脑和147例MS患者的血清，评估了血清自身抗体与表达可靠的成熟少突胶质细胞标志物Nogo-A的小鼠少突胶质细胞的结合情况，这些患者包括103例复发缓解型MS（RRMS）、22例继发进展型MS（SPMS）和22例原发进展型MS（PPMS）患者、38例视神经脊髓炎谱系障碍（NMOSD）患者、23例其他炎性神经系统疾病（OIND）患者和39例健康对照（HC）。使用从小鼠小脑提取的蛋白质和抗少突胶质细胞抗体阳性MS患者的IgG进行蛋白质印迹法（WB）检测。基于组织的IFA显示，抗少突胶质细胞抗体在3/22（13.6%）的PPMS患者和1/22（4.5%）的SPMS患者中呈阳性，但在RRMS、NMOSD和OIND患者或HC中未呈阳性。WB证明血清抗少突胶质细胞抗体识别的目标中枢神经系统蛋白约为110 kDa和/或150 kDa。与抗少突胶质细胞抗体阴性的MS患者相比，抗少突胶质细胞抗体阳性的MS患者在血清采样时年龄显著更大，在扩展残疾状态量表和多发性硬化症严重程度评分上得分显著更高，且精神障碍发生率更高。尽管由于抗少突胶质细胞抗体的频率较低，其临床意义仍不明确，但抗少突胶质细胞自身抗体是监测MS疾病病理和进展的潜在生物标志物。
