Distinct features of B cell receptors in neuromyelitis optica spectrum disorder among CNS inflammatory demyelinating diseases

Journal of Neuroinflammation

Research

Jinsung Noh¹  Hyori Kim²  Yonghee Lee³  Dayoung Seo⁴  Hyunji Kim⁴  Wangyong Shin⁴  Seungmi Kim⁴  Eun-Jae Lee⁵  Hyunjin Kim⁶  Young-Min Lim⁶  Jong-Eun Park⁷  Hyo Jae Kim⁷ 

[1] Bio-MAX Institute, Seoul National University, Seoul, South Korea;Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea;Department of Electrical and Computer Engineering, Seoul National University, Seoul, South Korea;Department of Medicine, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South Korea;Department of Medicine, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South Korea;Department of Neurology, Asan Medical Center, Ulsan University of Medicine, Seoul, South Korea;Department of Neurology, Asan Medical Center, Ulsan University of Medicine, Seoul, South Korea;Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea;

关键词: Inflammatory demyelinating disease of the CNS;    Neuromyelitis optica spectrum disorder;    Myelin oligodendrocyte glycoprotein antibody associated disease;    B cell;    B cell receptor;   

DOI  :  10.1186/s12974-023-02896-6

 received in 2023-08-01, accepted in 2023-09-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing.MethodsFrom a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups.ResultsBlood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups.ConclusionsNMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual’s lifetime.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 5

Fig. 1

Fig. 5

12951_2015_155_Article_IEq25.gif

Fig. 3

12951_2015_111_Article_IEq1.gif