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

被引：2

作者：

Kim, Hyo Jae ^{[1
]}

Park, Jong-Eun ^{[1
]}

Shin, Wangyong ^{[2
]}

Seo, Dayoung ^{[2
]}

Kim, Seungmi ^{[2
]}

Kim, Hyunji ^{[2
]}

Noh, Jinsung ^{[3
]}

Lee, Yonghee ^{[4
]}

Kim, Hyunjin ^{[5
]}

Lim, Young-Min ^{[5
]}

Kim, Hyori ^{[6
]}

Lee, Eun-Jae ^{[2
,5
]}

机构：

[1] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon, South Korea

[2] Univ Ulsan, Asan Med Inst Convergence Sci & Technol, Dept Med, Coll Med, Seoul, South Korea

[3] Seoul Natl Univ, BioMax Inst, Seoul, South Korea

[4] Seoul Natl Univ, Dept Elect & Comp Engn, Seoul, South Korea

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea

[6] Asan Med Ctr, Asan Inst Life Sci, Convergence Med Res Ctr, Seoul, South Korea

来源：

JOURNAL OF NEUROINFLAMMATION | 2023年 / 20卷 / 01期

关键词：

Inflammatory demyelinating disease of the CNS; Neuromyelitis optica spectrum disorder; Myelin oligodendrocyte glycoprotein antibody associated disease; B cell; B cell receptor; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; CEREBROSPINAL-FLUID; AUTOIMMUNE; DYNAMICS;

D O I：

10.1186/s12974-023-02896-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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.

引用

页数：11