Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Department of Medicine, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South Korea.
J Neuroinflammation. 2023 Oct 4;20(1):225. doi: 10.1186/s12974-023-02896-6.
Neuromyelitis 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.
From 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.
Blood 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.
NMOSD 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.
视神经脊髓炎谱系疾病（NMOSD）因其独特的疾病特征，包括严重的临床发作、广泛的病变以及与系统性自身免疫性疾病的关联，在中枢神经系统炎症性脱髓鞘疾病（CIDDs）中脱颖而出。我们旨在使用高通量测序研究 NMOSD 和其他 CIDDs 之间 B 细胞受体（BCR）的特征是否不同。
从一个前瞻性队列中，我们招募了 CIDDs 患者，并根据自身抗体的存在和类型进行分类：抗水通道蛋白-4 抗体阳性的 NMOSD、抗髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）、双阴性脱髓鞘疾病（DSN）和健康对照组（HCs）。分析和比较了不同疾病组之间的 BCR 特征，包括同种型类别、克隆性、体细胞高频突变（SHM）和第三互补决定区（CDR3）长度。
对 33 名 CIDDs 患者（13 名 NMOSD、12 名 MOGAD 和 8 名 DSN）和 34 名 HCs 的血液样本进行了 BCR 测序。与其他疾病组相比，NMOSD 患者的 BCR 特征更倾向于激活。他们表现出较低比例的未转换同种型（IgM 和 IgD）和较高比例的转换同种型（IgG）、BCR 克隆性增加、SHM 率升高和 CDR3 长度缩短。值得注意的是，年龄较大被确定为与 NMOSD 组中这些激活的 BCR 特征相关的临床因素，包括克隆性和 SHM 率的升高。相反，在其他 CIDD 组中，没有发现与激活的 BCR 特征相关的临床因素。
在 CIDDs 患者中，NMOSD 患者表现出最明显的 B 细胞激活，表现为更高水平的同种型类别转换、克隆性、SHM 率和更短的 CDR3 长度。这些发现表明，NMOSD 患者的 B 细胞介导的体液免疫反应和特征与其他 CIDDs 不同，包括 MOGAD。年龄被确定为与 NMOSD 中 BCR 激活相关的临床因素，这表明抗水通道蛋白-4 抗体引起的持续 B 细胞激活的重要性，即使在个体一生中没有临床复发的情况下也是如此。
