Peeters Liesbet M, Vanheusden Marjan, Somers Veerle, Van Wijmeersch Bart, Stinissen Piet, Broux Bieke, Hellings Niels
School of Life Sciences, Biomedical Research Institute, Hasselt University, Transnationale Universiteit Limburg, Diepenbeek, Belgium.
Front Immunol. 2017 Sep 20;8:1160. doi: 10.3389/fimmu.2017.01160. eCollection 2017.
Multiple sclerosis (MS) is the leading cause of chronic neurological disability in young adults. The clinical disease course of MS varies greatly between individuals, with some patients progressing much more rapidly than others, making prognosis almost impossible. We previously discovered that cytotoxic CD4+ T cells (CD4+ CTL), identified by the loss of CD28, are able to migrate to sites of inflammation and that they contribute to tissue damage. Furthermore, in an animal model for MS, we showed that these cells are correlated with inflammation, demyelination, and disability. Therefore, we hypothesize that CD4+ CTL drive progression of MS and have prognostic value. To support this hypothesis, we investigated whether CD4+ CTL are correlated with worse clinical outcome and evaluated the prognostic value of these cells in MS. To this end, the percentage of CD4+CD28null T cells was measured in the blood of 176 patients with relapsing-remitting MS (=baseline). Multimodal evoked potentials (EP) combining information on motoric, visual, and somatosensoric EP, as well as Kurtzke expanded disability status scale (EDSS) were used as outcome measurements at baseline and after 3 and 5 years. The baseline CD4+CD28null T cell percentage is associated with EP ( = 0.003, = 0.28), indicating a link between these cells and disease severity. In addition, the baseline CD4+CD28null T cell percentage has a prognostic value since it is associated with EP after 3 years ( = 0.005, = 0.29) and with EP and EDSS after 5 years ( = 0.008, = 0.42 and = 0.003, = 0.27). To the best of our knowledge, this study provides the first direct link between the presence of CD4+ CTL and MS disease severity, as well as its prognostic value. Therefore, we further elaborate on two important research perspectives: 1° investigating strategies to block or reverse pathways in the formation of these cells resulting in new treatments that slow down MS disease progression, 2° including immunophenotyping in prediction modeling studies to aim for personalized medicine.
多发性硬化症（MS）是年轻成年人慢性神经功能障碍的主要原因。MS的临床病程在个体之间差异很大，一些患者的病情进展比其他患者快得多，这使得预后几乎不可能预测。我们之前发现，通过CD28缺失鉴定的细胞毒性CD4 + T细胞（CD4 + CTL）能够迁移到炎症部位，并导致组织损伤。此外，在MS动物模型中，我们表明这些细胞与炎症、脱髓鞘和残疾相关。因此，我们假设CD4 + CTL驱动MS的进展并具有预后价值。为了支持这一假设，我们研究了CD4 + CTL是否与更差的临床结果相关，并评估了这些细胞在MS中的预后价值。为此，我们测量了176例复发缓解型MS患者（=基线）血液中CD4 + CD28null T细胞的百分比。在基线以及3年和5年后，使用结合运动、视觉和躯体感觉诱发电位（EP）信息的多模态诱发电位以及Kurtzke扩展残疾状态量表（EDSS）作为结果测量指标。基线CD4 + CD28null T细胞百分比与EP相关（= 0.003，= 0.28），表明这些细胞与疾病严重程度之间存在联系。此外，基线CD4 + CD28null T细胞百分比具有预后价值，因为它与3年后的EP相关（= 0.005，= 0.29）以及与5年后的EP和EDSS相关（= 0.008，= 0.42和= 0.003，= 0.27）。据我们所知，本研究首次提供了CD4 + CTL的存在与MS疾病严重程度及其预后价值之间的直接联系。因此，我们进一步阐述了两个重要的研究观点：1°研究阻断或逆转这些细胞形成途径的策略，从而产生减缓MS疾病进展的新疗法；2°在预测模型研究中纳入免疫表型分析，以实现个性化医疗。
