Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis
Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis
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DOI：
10.3389/fimmu.2020.00056
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发表时间：
2020-01-31
影响因子：
7.3
通讯作者：
Ziemssen, Tjalf
中科院分区：
文献类型：
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作者：
Akguen, Katja;Blankenburg, Judith;Ziemssen, Tjalf
背景资料：阿仑单抗是一种治疗多发性硬化症（MS）的高效药物，其特征在于特定的耗竭和再增殖模式。作为一种类似诱导的治疗概念，两个强制性输注疗程可以抑制大多数患者的长期疾病活动，额外的疗程可以成功地管理随后的疾病活动复发。目前，没有生物标志物来识别患者重新出现的疾病活动需要retreatment.Methods：在这项研究中，我们系统地描述了16 MS患者开始阿仑单抗。临床参数，MRI和详细的免疫分析进行了长达84 months.Results：阿仑单抗导致临床疾病的活动在所有评估的患者显着下降，每3个月。16例患者中有9例在长达84个月内没有疾病活动性（NEDA）证据（3）（“完全缓解者”），而7例患者显示临床或/和亚临床MRI疾病活动性并接受了Alemutzumab重新治疗（“部分缓解者”）。在两个缓解类别中，所有T和B细胞亚群在Alemtuzumab治疗后均显著耗竭。特别是，Th 1和Th 17细胞的绝对数量显着下降，并保持稳定低于基线水平，这种效果是特别明显的完全反应。虽然平均细胞数在组间没有显著差异，但事件驱动的免疫分析表明，从复发活动前6个月开始，Th 1和Th 17细胞的绝对数量显示出可重复的增加。这一变化似乎预测紧急疾病活动时，相比稳定diseases.Conclusion：需要研究更大的患者人群，以确认频繁的免疫分析可能有助于评估阿仑单抗再治疗的临床决策。
Background: Alemtuzumab is a highly effective drug for the treatment of multiple sclerosis (MS), characterized by specific patterns of depletion and repopulation. As an induction-like treatment concept, two mandatory infusion courses can inhibit long-term disease activity in the majority of patients, and additional courses can successfully manage subsequent re-emergence of disease activity. Currently, there are no biomarkers to identify patients with re-emergent disease activity requiring retreatment.Methods: In this study, we systematically characterized 16 MS patients commencing alemtuzumab. Clinical parameters, MRI and detailed immunoprofiling were conducted every 3 months for up to 84 months.Results: Alemtuzumab led to significant decrease in clinical disease activity in all evaluated patients. Nine out of 16 patients presented with no evidence of disease activity (NEDA)-3 up to 84 months ("complete-responder"), while 7 patients demonstrated clinical or/and subclinical MRI disease activity and received alemutzumab retreatment ("partial-responder"). In both response categories, all T- and B-cell subsets were markedly depleted after alemtuzumab therapy. In particular, absolute numbers of Th1 and Th17 cells were markedly decreased and remained stable below baseline levels-this effect was particularly pronounced in complete-responders. While mean cell numbers did not differ significantly between groups, analysis of event-driven immunoprofiling demonstrated that absolute numbers of Th1 and Th17 cells showed a reproducible increase starting 6 months before relapse activity. This change appears to predict emergent disease activity when compared with stable disease.Conclusion: Studies with larger patient populations are needed to confirm that frequent immunoprofiling may assist in evaluating clinical decision-making of alemtuzumab retreatment.