School of Medicine and Dentistry, Gold Coast Campus, Griffith University, Southport, QLD, Australia.
National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Southport, QLD, Australia.
J Neuroinflammation. 2024 Nov 1;21(1):281. doi: 10.1186/s12974-024-03263-9.
Secondary autoimmune disease (SAID) in the context of alemtuzumab treatment is one of the main safety concerns that may arise following administration in people with multiple sclerosis (pwMS). Contributing factors underlying this adverse event are not well understood. The purpose of this systematic review was to appraise the literature investigating the role of alemtuzumab in the development of SAID in pwMS following treatment and identify potential biomarkers/ risk factors that may be predictive of onset of this manifestation.
Relevant publications were retrieved from PubMed, Embase, and Web of Science using a three-pronged search strategy containing the following keywords: "multiple sclerosis"; "alemtuzumab"; and "autoimmunity". Studies that fulfilled the specified eligibility criteria and investigated SAID development after alemtuzumab in pwMS were included in the final analysis.
19 papers were included in the final review. Approximately, 47.92% of pwMS treated with alemtuzumab experienced SAID. A variety of biomarkers and risk factors were noted in the development of SAID, with a focus on immunological changes, including: increased homeostatic proliferation and T cell cycling, along with consistently elevated baseline serum IL-21 levels and thyroid autoantibodies. There was no significant association between known human leukocyte antigen (HLA) risk alleles, lymphocyte profile or dynamics and SAID development.
While the mechanism underlying SAID following alemtuzumab is not fully understood, potential biomarkers and risk factors that may assist in elucidating mechanisms underlying this phenomenon have been documented in several independent studies. Following immunodepletion from alemtuzumab, an IL-21 driven increase in homeostatic proliferation and T cell cycling may disrupt tolerance mechanisms leading to an increase in the propensity toward alemtuzumab-induced autoimmunity. Further research is necessary to clarify the physiological changes after alemtuzumab therapy that trigger SAID in pwMS.
在来氟米特治疗的情况下，继发性自身免疫性疾病（SAID）是多发性硬化症（pwMS）患者接受治疗后可能出现的主要安全问题之一。导致这种不良事件的因素尚不清楚。本系统评价的目的是评估文献，调查来氟米特在 pwMS 治疗后 SAID 发展中的作用，并确定可能预测这种表现发生的潜在生物标志物/危险因素。
使用包含以下关键字的三管齐下的搜索策略从 PubMed、Embase 和 Web of Science 中检索相关出版物：“多发性硬化症”；“来氟米特”；和“自身免疫”。符合指定纳入标准并研究来氟米特治疗后 pwMS 中 SAID 发展的研究被纳入最终分析。
最终综述包括 19 篇论文。约 47.92%接受来氟米特治疗的 pwMS 发生了 SAID。在 SAID 的发展中注意到了各种生物标志物和危险因素，重点是免疫变化，包括：固有增殖和 T 细胞循环增加，以及基线血清 IL-21 水平和甲状腺自身抗体持续升高。已知人类白细胞抗原（HLA）风险等位基因、淋巴细胞谱或动力学与 SAID 发展之间没有显著关联。
虽然来氟米特后 SAID 的机制尚不完全清楚，但在几项独立研究中已经记录了可能有助于阐明这种现象机制的潜在生物标志物和危险因素。在来氟米特引起的免疫耗竭后，IL-21 驱动的固有增殖和 T 细胞循环增加可能破坏耐受机制，导致来氟米特诱导自身免疫的倾向增加。需要进一步研究来阐明来氟米特治疗后引发 pwMS 中 SAID 的生理变化。
