Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (microarray). Homo sapiens

Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab. Overall design: We used unbiased whole blood transcriptomic approaches to identify cellular and molecular markers that accompany successful treatment with a non-Fc binding anti-CD3 antibody (teplizumab)

在其他自身免疫疾病背景中展现活性的生物制剂，在初诊1型糖尿病（type 1 diabetes, T1D）患者中的疗效存在显著差异：针对多治疗靶点的干预虽可使部分患者的C肽水平出现短暂稳定，但后续疾病进展速率与对照组完全一致。目前学界尚未明确，为何不同的治疗方案会带来相似的临床病程。本研究采用整合系统生物学与流式细胞术（flow cytometry）手段，旨在阐明接受抗CD3单克隆抗体（anti-CD3 monoclonal antibody）teplizumab治疗的T1D患者中，与C肽水平稳定相关的免疫机制。研究设计：本研究通过无偏倚全血转录组学方法，筛选伴随非Fc结合型抗CD3抗体（teplizumab）成功治疗过程的细胞与分子标志物。