文摘
摘要目的:PD-1 / PD-L1(程序性细胞死亡蛋白1 /细胞程序性死亡配体1)轴适应性免疫系统中起着重要的作用,并影响肿瘤和炎症性疾病。的角色PD-1 / PD-L1轴在多发性硬化症(MS)尚未详细调查。我们旨在描绘不同的表达模式在外周血单核细胞(PBMC)子集和评估的角色上下文中的可溶性PD-1 / PD-L1女士。
背景:PD-L1 / PD-1还以可溶形式存在(sPD-L1 / sPD-1)从细胞表面流。在系统性自身免疫性疾病,sPD-1 / sPD-L1血清水平和膜结合PD-1 / PD-L1 T和抗原递呈细胞都与疾病活动和治疗反应。在女士,PD-1 / PD-L1轴,特别是可溶性的角色PD-1 / PD-L1知之甚少但可能提供相关性疾病标记和潜在的治疗目标。
设计/方法:深度immunophenotyping通过流式细胞术进行PBMCs 49岁的患者复发缓和女士(名RRMS)和27个控件。sPD-1 / sPD-L1血清水平分析了一群84名RRMS患者和36的控制。评估的治疗潜力可溶性PD-L1 600μg /公斤实验性自身免疫性脑脊髓炎重组蛋白是系统管理(运算单元),女士的动物模型。
结果:名RRMS患者显示不同的细胞PD-1 / PD-L1 PBMCs表达模式和一个协会sPD-L1女士亚型和疾病严重程度。导致系统性管理重组PD-L1实验性自身免疫性脑脊髓炎改善疾病的严重程度和减少外周免疫细胞的渗透进入中枢神经系统。
结论:的显著表达PD-1 / PD-L1名RRMS患者免疫细胞的子集,和sPD-L1与疾病严重程度的相关性提供了潜力的使用作为一个血清标志物在此外,女士的背景下增强coregulatory PD-1 / PD-L1信号通过外源性补充sPD-L1可能作为一种新的治疗策略严重的急性神经炎症阶段。
披露:Tsaktanis博士没有披露。Linnerbauer先生没有披露。Loesslein太太没有披露。缝边器收到了教授个人补偿的范围0 - 499美元为Vaccitech担任顾问。缝边器收到了教授的个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会诺华。缝边器收到了教授的个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会Polpharma。缝边器收到了教授的个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会TG疗法。缝边器收到了教授个人补偿的范围0 - 499美元为科学顾问或服务数据安全监测委员会过敏治疗。缝边器收到了教授研究的机构Regeneron的支持。缝边器收到了教授研究的机构来自德国研究基金会的支持。 The institution of Prof. Hemmer has received research support from German Ministry for Education and Research. The institution of Prof. Hemmer has received research support from European Commission. Prof. Hemmer has received intellectual property interests from a discovery or technology relating to health care. Prof. Hemmer has received intellectual property interests from a discovery or technology relating to health care. Mark Mühlau has nothing to disclose. Dr. Quintana has nothing to disclose. Prof. Rothhammer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Rothhammer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Prof. Rothhammer has received research support from German Research Foundation. The institution of Prof. Rothhammer has received research support from European Research Council.
