Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy.
Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy.
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DOI：
10.1016/j.jaut.2009.10.005
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发表时间：
2010-06
影响因子：
12.8
通讯作者：
Bianchine P
中科院分区：
文献类型：
--
作者：
Orban T;Farkas K;Jalahej H;Kis J;Treszl A;Falk B;Reijonen H;Wolfsdorf J;Ricker A;Matthews JB;Tchao N;Sayre P;Bianchine P
越来越多的证据表明，在1型糖尿病（T1DM）中观察到的自身免疫是自身攻击性细胞亚群和调节性细胞亚群之间失衡的结果。因此，补充或增强现有监管子集的治疗药物是该适应症中备受追捧的目标。在这里，我们报告了一项双盲、安慰剂对照、I期临床试验的结果，该试验在12例最近诊断为T1DM的受试者中进行了一项新的抗原特异性治疗。我们的主要目的是测试它的安全性。研究药物人胰岛素B链不完全弗氏佐剂（IFA）单次肌内注射给药，受试者随访2年。所有受试者均完成治疗和所有随访访视。该疗法通常是安全的，耐受性良好。每6个月测量一次混合餐刺激的C肽反应，两组之间无统计学差异。所有接种自身抗原的患者，但没有接受安慰剂的患者，都产生了强烈的胰岛素特异性体液和T细胞应答。单次注射后长达两年，在实验组受试者（而非对照组受试者）的外周血中，可以分离和克隆胰岛素B链特异性CD4+ T细胞，其显示出调节性T细胞的表型和功能特征。诱导产生自身抗原特异性调节性T细胞的持久、稳健的免疫应答为进一步测试1型糖尿病中的该疗法提供了强有力的理由。（clinicaltrials.gov标识符NCT00057499）。
There is a growing body of evidence to suggest that the autoimmunity observed in type 1 diabetes mellitus (T1DM) is the result of an imbalance between autoaggressive and regulatory cell subsets. Therapeutics that supplement or enhance the existing regulatory subset are therefore a much sought after goal in this indication. Here, we report the results of a double blind, placebo controlled, phase I clinical trial of a novel antigen-specific therapeutic in 12 subjects with recently diagnosed T1DM. Our primary objective was to test its safety. The study drug, human insulin B-chain in incomplete Freund’s adjuvant (IFA) was administered as a single intramuscular injection, with subjects followed for 2 years. All subjects completed therapy and all follow-up visits. The therapy was generally safe and well-tolerated. Mixed meal stimulated C-peptide responses, measured every 6 months, showed no statistical differences between arms. All patients vaccinated with the autoantigen, but none who received placebo, developed robust insulin-specific humoral and T cell responses. Up to two years following the single injection, in peripheral blood from subjects in the experimental arm, but not the control arm, insulin B-chain-specific CD4+ T cells could be isolated and cloned that showed phenotypic and functional characteristics of regulatory T cells. The induction of a lasting, robust immune response generating autoantigen-specific regulatory T cells provides strong justification for further testing of this therapy in type 1 diabetes. (clinicaltrials.gov identifier NCT00057499).
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影响因子：
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通讯作者：
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