背景:共信号和粘附分子是在T淋巴细胞和抗原呈递细胞之间产生免疫突触的重要元素;它们正或负调节T细胞受体与其同源抗原之间的相互作用,由主要的组织相容性复合体提出。
目的:我们对多发性硬化症(MS)的高疗效疾病修饰药物(HEDMD)对形成免疫突触的共信号和粘附分子的影响进行了系统评价。
方法:我们搜索了EMBASE,MEDLINE,和其他来源,以确定有关HEDMDs对参与MS或其他自身免疫性疾病患者免疫突触形成的共信号传导和粘附分子的影响的临床或临床前报告。我们包括克拉屈滨片的报告,抗CD20单克隆抗体,S1P调制器,布鲁顿酪氨酸激酶抑制剂,和那他珠单抗.
结果:在7340份出版物中的56份合格报告中,发现了有限的相关证据。并不是所有的共信号和粘附分子都被研究过与每一个HEDMD有关,有更多的数据是关于抗CD20单克隆抗体(影响CD80,CD86,GITR和TIGIT),克拉屈滨片剂(影响CD28,CD40,ICAM-1,LFA-1)和S1P调节剂(影响CD86,ICAM-1和LFA-1),对纳他珠单抗(影响CD80,CD86,CD40,LFA-1,VLA-4)和Alemtuzumab(影响GITR和CTLA-4)较少。
结论:HEDMD对免疫突触的影响还远未完成。现有证据表明,药物之间存在区别差异,值得进一步研究。
BACKGROUND: Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex.
OBJECTIVE: We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse.
METHODS: We searched EMBASE, MEDLINE, and other sources to identify clinical or preclinical reports on the effects of HEDMDs on co-signaling and adhesion molecules that participate in the formation of immune synapses in patients with MS or other autoimmune disorders. We included reports on cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors of Bruton\'s Tyrosine Kinase, and natalizumab.
RESULTS: In 56 eligible reports among 7340 total publications, limited relevant evidence was uncovered. Not all co-signaling and adhesion molecules have been studied in relation to every HEDMD, with more data being available on the anti-CD20 monoclonal antibodies (that affect CD80, CD86, GITR and TIGIT), cladribine tablets (affecting CD28, CD40, ICAM-1, LFA-1) and the S1P modulators (affecting CD86, ICAM-1 and LFA-1) and less on Natalizumab (affecting CD80, CD86, CD40, LFA-1, VLA-4) and Alemtuzumab (affecting GITR and CTLA-4).
CONCLUSIONS: The puzzle of HEDMD effects on the immune synapse is far from complete. The available evidence suggests that distinguishing differences exist between drugs and are worth pursuing further.