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多发性硬化症中的髓反应性TCR/IgM双表达体淋巴细胞:将病原发生与抗CD20疗法联系起来

Prajita Paul¹, Marjan Behzadirad¹, Rafid Al Hallaf¹

¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Immunological investigations

|September 17, 2025

概括

双表达细胞 (DE) 是一种新型的淋巴细胞群,在多发性硬化症 (MS) 患者中发现的频率更高,对髓抗原有反应. 这些DEs被抗CD20疗法所耗尽,为MS治疗提供了新的见解.

科学领域:

免疫学免疫学免疫学
神经免疫学神经免疫学

背景情况:

多发性硬化症 (MS) 是一种自身免疫性疾病,主要与T细胞有关,但有效的治疗方法针对B细胞,创造了一个治疗悖论.
双表达细胞 (DE) 是一种新发现的淋巴细胞群体,共同表达T细胞受体 (TCRαβ) 和B细胞受体 (BCRs),与MS的发病有关.
DEs可能代表MS中T和B细胞反应之间的关键联系,并且可能是抗CD20疗法的意外目标.

研究的目的:

在复发性复发性硬化症 (RRMS) 患者中识别和描述双表达细胞 (DE).
调查DE在MS病变发生过程中的作用,包括它们对髓自身抗原的反应.
确定DE对抗CD20疾病修饰疗法 (DMT) 的易感性.

主要方法:

来自RRMS患者和健康对照者的外周血液和脑脊液 (CSF) 的分析.
DEs的表型和功能特征,包括T细胞受体 (TCR) 和B细胞受体 (BCR) 表达.
评估DE对髓自身抗原的反应及其通过ocrelizumab的消耗在试点队列中的评估.

主要成果:

与对照人群相比,在RRMS患者的外周血液和CSF中发现DE的频率显著更高.
脑脊液中的DE显示高CD20表达 (高达95%) 和CXCR3表达,表明参与免疫细胞招募.
在RRMS患者中,DEs对髓自身抗原有强烈的反应,并且在ocrelizumab治疗后显著耗尽.

结论:

双表达细胞 (DE) 参与了多发性硬化症 (MS) 的发病.
这些发现为MS中抗CD20疗法的疗效提供了潜在的解释,MS是一种传统上被认为是T细胞驱动的疾病.
DEs代表了一个新的治疗目标,也是理解多发性硬化症免疫病理学的关键因素.

关键词:

多发性硬化症是多发性硬化症.抗CD20的疾病修饰疗法 (DMT)大脑脊髓液 (CSF) 是一种双表达体 (DE) 淋巴细胞

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