Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.
Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.
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DOI：
10.1038/s41590-020-0744-z
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发表时间：
2020-10
影响因子：
30.5
通讯作者：
Walker LSK
中科院分区：
文献类型：
--
作者：
Edner NM;Heuts F;Thomas N;Wang CJ;Petersone L;Kenefeck R;Kogimtzis A;Ovcinnikovs V;Ross EM;Ntavli E;Elfaki Y;Eichmann M;Baptista R;Ambery P;Jermutus L;Peakman M;Rosenthal M;Walker LSK
滤泡辅助性T细胞(TFH)与1型糖尿病(T1D)有关，其发生与CD28共刺激有关。我们在糖尿病小鼠模型和新发的T1D患者中，测试了使用CTLA-4-Ig融合蛋白(Abatacept)的共刺激阻断是否降低了Tfh。无偏倚的生物信息学分析表明，ICOS+Tfh和包括T-外周辅助细胞在内的其他ICOS+群体对共刺激阻断高度敏感。我们能够使用治疗前的TFH谱来推导出一个模型，该模型可以预测患有T1D的患者对阿巴西普的临床反应。使用两种独立的方法，我们证明了基线时ICOS+Tfh的较高频率与服用阿巴达塞后的临床反应较差有关。因此，TFH分析可能代表了一种新的分层工具，允许识别最有可能从共刺激阻断中受益的个人。
Follicular helper T cells (Tfh) are implicated in type 1 diabetes (T1D) and their development has been linked to CD28 costimulation. We tested whether Tfh were decreased by costimulation blockade using the CTLA-4-Ig fusion protein (Abatacept) in a mouse model of diabetes and in individuals with new onset T1D. Unbiased bioinformatic analysis identified that ICOS+ Tfh, and other ICOS+ populations including T-peripheral helper cells, were highly sensitive to costimulation blockade. We were able to use pre-treatment Tfh profiles to derive a model that could predict clinical response to Abatacept in individuals with T1D. Using two independent approaches we demonstrated that higher frequencies of ICOS+ Tfh at baseline were associated with a poor clinical response following Abatacept administration. Tfh analysis may therefore represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.
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影响因子：
8.2
作者：
Ekman, Ilse;Ihantola, Emmi-Leena;Kinnunen, Tuure
通讯作者：
Kinnunen, Tuure
影响因子：
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作者：
Leete, Pia;Willcox, Abby;Morgan, Noel G.
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DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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影响因子：
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作者：
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Gladman DD
影响因子：
4.4
作者：
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通讯作者：
Walker, Lucy S. K.