Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab
Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab
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DOI：
10.1172/jci.insight.93222
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发表时间：
2017-06-15
期刊：
影响因子：
8
通讯作者：
Wrammert, Jens
中科院分区：
文献类型：
--
作者：
Cho, Alice;Bradley, Bridget;Wrammert, Jens
利妥昔单抗是一种治疗性抗CD20单抗，广泛用于治疗B细胞淋巴瘤和自身免疫性疾病，如风湿性关节炎、系统性红斑狼疮和自身免疫性水疱性皮肤病(AIBD)。虽然利妥昔单抗可以完全耗尽外周血中的B细胞，但目前尚不清楚一些先前存在的B细胞对病原体或疫苗的记忆是否会在耗竭中幸存下来，特别是在淋巴组织中，以及这些记忆B细胞在耗竭后的恢复过程中是否会经历自我平衡的扩张。在这种情况下，有关疫苗效力的有限数据来自同时接受化疗或其他有效免疫抑制剂的利妥昔单抗治疗的患者。在这里，我们提出了一项对AIBD患者季节性流感疫苗反应的深入分析，这些患者以前接受过利妥昔单抗治疗，通常没有接受额外的治疗干预。我们发现，尽管血液中缺乏流感特异性记忆B细胞，但患者对疫苗接种的强烈回忆反应，在细胞和血清学水平上都与健康对照组相当。对浆母细胞反应的谱系分析表明，它们可能来自不同的组织驻留记忆细胞池，难以耗尽。总体而言，这些数据对于为AIBD患者建立有效的疫苗接种时间表和一般使用利妥昔单抗治疗的患者的临床护理具有重要意义，并有助于我们对维持正常和致病的人类B细胞记忆的基本理解。
Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion. The limited data available on vaccine efficacy in this setting have been derived from rituximab-treated patients receiving concomitant chemotherapy or other potent immunosuppressants. Here, we present an in-depth analysis of seasonal influenza vaccine responses in AIBD patients previously treated with rituximab, who generally did not receive additional therapeutic interventions. We found that, despite a lack of influenza-specific memory B cells in the blood, patients mount robust recall responses to vaccination, comparable to healthy controls, both at a cellular and a serological level. Repertoire analyses of plasmablast responses suggest that they likely derive from a diverse pool of tissue-resident memory cells, refractory to depletion. Overall, these data have important implications for establishing an effective vaccine schedule for AIBD patients and the clinical care of rituximab-treated patients in general and contribute to our basic understanding of maintenance of normal and pathogenic human B cell memory.