The role of alemtuzumab in the development of secondary autoimmunity in multiple Sclerosis: a systematic review.

IF 9.3 1区医学 Q1 IMMUNOLOGY Journal of Neuroinflammation Pub Date : 2024-11-01 DOI:10.1186/s12974-024-03263-9

Sofia Jimenez-Sanchez, Rebekah Maksoud, Natalie Eaton-Fitch, Sonya Marshall-Gradisnik, Simon A Broadley

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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阿仑妥珠单抗在多发性硬化症继发性自身免疫发展中的作用：系统性综述。

背景：阿仑妥珠单抗治疗中的继发性自身免疫性疾病（SAID）是多发性硬化症患者（pwMS）用药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十分清楚。本系统性综述的目的是评估研究阿利珠单抗在多发性硬化症患者治疗后出现 SAID 的文献，并确定可能预测这种表现的潜在生物标志物/风险因素：使用包含以下关键词的三重搜索策略从 PubMed、Embase 和 Web of Science 检索相关出版物："多发性硬化症"、"阿仑珠单抗 "和 "自身免疫"。符合特定资格标准并调查了阿仑珠单抗治疗帕金森病后SAID发展情况的研究被纳入最终分析：19篇论文被纳入最终审查。约有 47.92% 接受阿仑珠单抗治疗的 pwMS 出现了 SAID。SAID的发生有多种生物标志物和风险因素，重点是免疫学变化，包括：同源增殖和T细胞循环增加，以及血清IL-21水平和甲状腺自身抗体基线持续升高。已知的人类白细胞抗原（HLA）风险等位基因、淋巴细胞特征或动态与SAID的发生无明显关联：结论：虽然阿仑珠单抗引发SAID的机制尚未完全明了，但多项独立研究已记录了可能有助于阐明这一现象发生机制的潜在生物标志物和风险因素。在阿仑珠单抗的免疫清除后，IL-21 驱动的同源性增殖和 T 细胞循环的增加可能会破坏耐受机制，导致阿仑珠单抗诱导的自身免疫倾向增加。有必要开展进一步的研究，以明确阿仑珠单抗治疗后引发 pwMS SAID 的生理变化。

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来源期刊

Journal of Neuroinflammation 医学-神经科学

CiteScore

15.90

自引率

3.20%

发文量

276

审稿时长

1 months

期刊介绍： The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes. Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems. The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.