Abstract

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.

Highlights

  • Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disease of the central nervous system (CNS) and the leading cause of neurologic disability in young adults [1]

  • We focused on the characteristics of Relapsing-remitting multiple sclerosis (RRMS) and MOGAD based on the three immune cell clusters in the above analysis

  • The results showed that three monocyte subsets, classical (CD14++ CD16−), nonclassical (CD14+ CD16++), and intermediate (CD14++ CD16+) monocytes, were identified based on the distinct markers, which were observed to be shared among all subjects (Figures 2A,B)

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Summary

Introduction

Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disease of the central nervous system (CNS) and the leading cause of neurologic disability in young adults [1]. ∼30–300 per 100,000 adults are affected with MS, leading to a substantial economic burden on healthcare systems and societies [2, 3]. MS repertoire manifests pathological characteristics of inflammation, demyelination, and axonal damage in the CNS. Among MS, relapsing-remitting MS (RRMS) is the most common type, accounting for nearly 85% of the initial diagnoses [4,5,6]. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly classified. Single-Cell Transcriptome of Neuroinflammation inflammatory demyelinating disease of CNS that shares clinical manifestations with RRMS [7,8,9,10].

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