抗sars - cov -2 t干细胞记忆在ocrelizumab治疗的MS患者中持续存在。

IF 5
Gisella Guerrera, Alessandra Mandelli, Annamaria Finardi, Mario Orrico, Silvia D'Orso, Mario Picozza, Maddalena Noviello, Valeria Beretta, Bruno Bonetti, Massimiliano Calabrese, Damiano Marastoni, Nicola De Rossi, Ruggero Capra, Marco Salvetti, Maria Chiara Buscarinu, Matilde Inglese, Antonio Uccelli, Lucia Moiola, Catarina Raposo, Erwan Muros-Le Rouzic, Rosetta Pedotti, Massimo Filippi, Chiara Bonini, Luca Battistini, Giovanna Borsellino, Roberto Furlan
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引用次数: 6

摘要

背景:ocrelizumab治疗多发性硬化症(pwMS)患者抗严重急性呼吸综合征冠状病毒2 (SARS-CoV2) t细胞反应的长期发展受到质疑。目的:探讨ocrelizumab治疗的pwMS感染SARS-CoV-2后的抗病毒t细胞反应。对照组包括ocrelizumab治疗的未感染SARS-CoV-2的pwMS,以及有或没有SARS-CoV-2感染的非ms个体。方法:用SARS-CoV-2肽池刺激外周血单个核细胞,用ELISPOT检测干扰素(IFN)-γ评估t细胞的反应性,用多参数荧光活化细胞分选(FACS)分析评估和表征t细胞的活化。结果:针对SARS-CoV-2刺突和N蛋白的ELISPOT检测在28/29(96%)接受奥克雷珠单抗治疗并感染SARS-CoV-2的pwMS中显示出特异性t细胞反应性,与未感染ms的患者相似,这种反应性在感染1年后存在,与输注奥克雷珠单抗的时间无关。在SARS-CoV-2肽池刺激后的FACS分析显示,在这些个体中,CD4+和CD8+ t细胞亚群中分别有96%和92%的激活诱导标记物(AIMs)存在。在naïve AIM+ CD4+和CD8+ T细胞中,我们检测到T记忆干细胞,表明获得了长期记忆。结论:使用ocrelizumab去除b细胞不会损害长期抗sars - cov -2 t细胞反应的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients.

Background: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned.

Objective: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection.

Methods: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation.

Results: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory.

Conclusions: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.

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