Neuron-binding antibody responses are associated with Black ethnicity in multiple sclerosis during natalizumab treatment.
Neuron-binding antibody responses are associated with Black ethnicity in multiple sclerosis during natalizumab treatment.
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DOI：
10.1093/braincomms/fcad218
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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多发性硬化症是一种中枢神经系统炎症退行性疾病，可能导致衰弱性残疾。过去二十年的几项研究表明，与白人相比，黑人或拉丁美洲人的多发性硬化症表现为快速、更致残的病程。然而，人们对可能导致这种与种族相关的不一致的临床严重程度的免疫学基础知之甚少。鉴于 B 细胞对多发性硬化症病理生理学的重要性，以及先前的研究显示，与白人多发性硬化症患者相比，黑人多发性硬化症患者脑脊液中的抗体水平有所增加，我们进行了一项队列研究，根据自我报告的种族和遗传血统随时间的推移确定 B 细胞亚群动态。此外，我们还确定了种族、血统和神经元结合 IgG 水平之间的关系。我们发现黑人种族与 B 细胞亚群（包括记忆 B 细胞）类别转换频率升高之间存在显着关联。双阴性两个B细胞；和抗体分泌细胞。这些子集的频率与西非遗传血统呈正相关。我们还观察到黑人种族与 IgG 与神经元结合增加之间存在显着关联。我们的数据表明，在非洲黑人侨民中患有多发性硬化症的个体中，T 细胞依赖性 B 细胞反应显着增强，表现出神经元结合抗体滴度的增加。驱动这种免疫生物学的因素可能会促进黑人和拉丁美洲多发性硬化症患者更常见的脱髓鞘、中枢神经系统萎缩和残疾。黑人患者所表现出的多发性硬化症严重程度的升高尚未得到充分研究。泰勒斯福德等人。报告称，自我报告的黑人种族与循环 B 细胞水平以及与中枢神经系统神经元结合的抗体增加有关。 B 细胞活性增加可能会导致黑人患者多发性硬化症的严重程度升高。
Multiple sclerosis is an inflammatory degenerative condition of the central nervous system that may result in debilitating disability. Several studies over the past twenty years suggest that multiple sclerosis manifests with a rapid, more disabling disease course among individuals identifying with Black or Latin American ethnicity relative to those of White ethnicity. However, very little is known about immunologic underpinnings that may contribute to this ethnicity-associated discordant clinical severity. Given the importance of B cells to multiple sclerosis pathophysiology, and prior work showing increased antibody levels in the cerebrospinal fluid of Black-identifying, compared to White-identifying multiple sclerosis patients, we conducted a cohort study to determine B cell subset dynamics according to both self-reported ethnicity and genetic ancestry over time. Further, we determined relationships between ethnicity, ancestry, and neuron-binding IgG levels. We found significant associations between Black ethnicity and elevated frequencies of class-switched B cell subsets, including memory B cells; double negative two B cells; and antibody-secreting cells. The frequencies of these subsets positively correlated with West African genetic ancestry. We also observed significant associations between Black ethnicity and increased IgG binding to neurons. Our data suggests significantly heightened T cell-dependent B cell responses exhibiting increased titres of neuron-binding antibodies among individuals with multiple sclerosis identifying with the Black African diaspora. Factors driving this immunobiology may promote the greater demyelination, central nervous system atrophy and disability more often experienced by Black-, and Latin American-identifying individuals with multiple sclerosis. Heightened multiple sclerosis severity exhibited by Black-identifying patients is understudied. Telesford et al. report that self-reported Black ethnicity is associated with increased circulating B cell levels, and antibodies that bind to central nervous system neurons. Increased B cell activity may contribute to heightened multiple sclerosis severity for Black-identifying patients.
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影响因子：
3.9
作者：
Kosoy, Roman;Nassir, Rami;Tian, Chao;White, Phoebe A.;Butler, Lesley M.;Silva, Gabriel;Kittles, Rick;Alarcon-Riquelme, Marta E.;Gregersen, Peter K.;Belmont, John W.;De La Vega, Francisco M.;Seldin, Michael F.
通讯作者：
Seldin, Michael F.
影响因子：
4
作者：
Amezcua, Lilyana;Conti, David V.;Liu, Lihua;Ledezma, Karina;Langer-Gould, Annette M.
通讯作者：
Langer-Gould, Annette M.
影响因子：
158.5
作者：
Hauser, S. L.;Bar-Or, A.;Kappos, L.
通讯作者：
Kappos, L.
影响因子：
12.7
作者：
Blauth, Kevin;Soltys, John;Owens, Gregory P.
通讯作者：
Owens, Gregory P.
影响因子：
14.5
作者：
Cepok, S;Rosche, B;Hemmer, B
通讯作者：
Hemmer, B