Table_3_Single-Cell Transcriptome Profiling Unravels Distinct Peripheral Blood Immune Cell Signatures of RRMS and MOG Antibody-Associated Disease.xlsx

Relapsing-remitting multiple sclerosis (RRMS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) are inflammatory demyelinating diseases of the central nervous system (CNS). Due to the shared clinical manifestations, detection of disease-specific serum antibody of the two diseases is currently considered as the gold standard for the diagnosis; however, the serum antibody levels are unpredictable during different stages of the two diseases. Herein, peripheral blood single-cell transcriptome was used to unveil distinct immune cell signatures of the two diseases, with the aim to provide predictive discrimination. Single-cell RNA sequencing (scRNA-seq) was conducted on the peripheral blood from three subjects, i.e., one patient with RRMS, one patient with MOGAD, and one patient with healthy control. The results showed that the CD19+ CXCR4+ naive B cell subsets were significantly expanded in both RRMS and MOGAD, which was verified by flow cytometry. More importantly, RRMS single-cell transcriptomic was characterized by increased naive CD8+ T cells and cytotoxic memory-like Natural Killer (NK) cells, together with decreased inflammatory monocytes, whereas MOGAD exhibited increased inflammatory monocytes and cytotoxic CD8 effector T cells, coupled with decreased plasma cells and memory B cells. Collectively, our findings indicate that the two diseases exhibit distinct immune cell signatures, which allows for highly predictive discrimination of the two diseases and paves a novel avenue for diagnosis and therapy of neuroinflammatory diseases.

复发缓解型多发性硬化（Relapsing-remitting multiple sclerosis, RRMS）与髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein, MOG）抗体相关疾病（MOGAD）均属于中枢神经系统（central nervous system, CNS）炎性脱髓鞘疾病。由于二者临床表现存在重叠，目前检测两种疾病的疾病特异性血清抗体被视为诊断金标准；然而，在两种疾病的不同病程阶段，血清抗体水平往往难以预测。本研究借助外周血单细胞转录组（single-cell transcriptome）分析，揭示了两种疾病各自独特的免疫细胞特征，旨在实现二者的精准鉴别诊断。研究团队对3名受试者的外周血开展了单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），受试者分别为1名复发缓解型多发性硬化患者、1名MOG抗体相关疾病患者及1名健康对照者。结果显示，CD19+ CXCR4+初始B细胞亚群在复发缓解型多发性硬化与MOG抗体相关疾病中均显著扩增，该发现经流式细胞术（flow cytometry）验证。更为重要的是，复发缓解型多发性硬化的单细胞转录组特征为初始CD8+ T细胞与细胞毒性记忆样自然杀伤（Natural Killer, NK）细胞增多，同时炎性单核细胞减少；而MOG抗体相关疾病则表现为炎性单核细胞与细胞毒性CD8+效应T细胞增多，同时浆细胞与记忆B细胞减少。综上，本研究结果表明两种疾病具有截然不同的免疫细胞特征，可实现二者的高精准鉴别诊断，为神经炎性疾病的诊断与治疗开辟了全新途径。