Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease
Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease
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DOI：
10.1126/sciadv.aaw7756
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发表时间：
2019-08-01
期刊：
影响因子：
13.6
通讯作者：
Anderson, Robert P.
中科院分区：
文献类型：
--
作者：
Goel, Gautam;Tye-Din, Jason A.;Anderson, Robert P.
乳糜泻（CeD）是由对谷物麸质的免疫反应引起的，可以用麸质消除饮食来治疗.在麸质暴露的数小时内，无论是经口还是经皮内注射的口外，接受治疗的患者都会出现胃肠道症状。为了测试麸质暴露是否导致与症状相关的全身性细胞因子产生时间，在麸质激发后在CeD患者中获得一系列多重细胞因子测量。肽注射升高了至少15种血浆细胞因子，其中IL-2、IL-8和IL-10最显著（在4小时时的倍数变化分别增加272、11和1.2）。IL-2和IL-8是在症状发作前2小时升高的唯一细胞因子。在麸质摄入后，IL-2是最早和最显著的细胞因子（在4小时时变化15倍）。在患者来源的谷蛋白特异性T细胞克隆和原代淋巴细胞研究的支持下，我们的观察结果表明，谷蛋白特异性CD 4（+）T细胞通过抗原暴露迅速再活化，可能导致CeD相关的胃肠道症状。
Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4(+) T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.