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首页> 外文期刊>Lancet Neurology >The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+T lymphocytes as pathogenic effectors and therapeutic targets
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The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+T lymphocytes as pathogenic effectors and therapeutic targets

机译：寻找多发性硬化症的靶抗原，第1部分：自身致病的CD4 + T淋巴细胞作为致病因子和治疗靶标

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摘要

Identification of the target antigens of pathogenic antibodies and T cells is of fundamental importance for understanding the pathogenesis of multiple sclerosis, and for the development of personalised treatments for the disease. Myelin-specific CD4+ T cells emerged long ago as a key player in animal models of multiple sclerosis. Taking a forward-translational approach, autoreactive CD4+ T cells have been studied extensively in patients with multiple sclerosis, and there is evidence, but as yet no direct proof, that autoreactive CD4+ T cells are a key player in the pathogenesis of the disorder. Several therapies that selectively target myelin-specific CD4+ T cells have been investigated in clinical trials up to phase 3. So far, however, none of these (mostly underpowered) therapeutic trials have provided definitive evidence of clinical efficacy. One major obstacle to personalised, highly selective immunotherapy is the absence of standardised and reliable assays to assess antigen-specific human T-cell responses. Such assays would be essential for stratification of patients with multiple sclerosis according to their individual target antigens.
机译：鉴定病原性抗体和T细胞的靶抗原对于理解多发性硬化症的发病机理以及开发针对该疾病的个性化治疗至关重要。髓磷脂特异性CD4 + T细胞早在多发性硬化症动物模型中就已发挥了关键作用。采用正向翻译方法，已经对多发性硬化症患者的自身反应性CD4 + T细胞进行了广泛研究，并且有证据，但尚无直接证据表明，自身反应性CD4 + T细胞是该病发病机制的关键因素。直到第3阶段的临床试验中，已经研究了几种选择性靶向髓鞘特异性CD4 + T细胞的疗法，但是，到目前为止，这些疗法（大多数功能不足）都没有提供临床疗效的明确证据。个性化，高度选择性免疫疗法的主要障碍之一是缺乏标准化和可靠的测定方法来评估抗原特异性人T细胞反应。此类测定对于根据多发性硬化症患者的各自靶抗原进行分层至关重要。

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