在乳糜泻中，麦胶特异性 T 细胞上的 CD38 表达是 gluten 再暴露的强有力标志物。
CD38 expression on gluten-specific T cells is a robust marker of gluten re-exposure in coeliac disease.
机构信息
K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway.
Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
出版信息
United European Gastroenterol J. 2019 Dec;7(10):1337-1344. doi: 10.1177/2050640619874183. Epub 2019 Sep 7.
BACKGROUND
Increasing efforts are being put into new treatment options for coeliac disease (CeD), a chronic disorder of the small intestine induced by gluten. Interleukin-2 (IL-2) and gluten-specific CD4 + T cells increase in the blood after four hours and six days, respectively, following a gluten challenge in CeD patients. These responses are unique to CeD and are not seen in controls. We aimed to evaluate different markers reflecting a recall response to gluten exposure that may be used to monitor therapy.
METHODS
CeD patients on a gluten-free diet underwent a one- ( = 6) or three-day ( = 7) oral gluten challenges. We collected blood samples at several time points between baseline and day 8, and monitored gluten-specific CD4 + T cells for their frequency and CD38 expression using HLA-DQ:gluten tetramers. We assessed the IL-2 concentration in plasma four hours after the first gluten intake.
RESULTS
The frequency of gut-homing, tetramer-binding, CD4 + effector memory T (tetramer + β7 + T) cells and the IL-2 concentration measured shortly after the first dose of gluten increased significantly after the one- and three-day gluten challenges, but large interindividual differences were exhibited. The frequency of tetramer + β7 + T plateaued between days 6 and 8 and was lower after the one-day challenge. We observed a consistent increase in CD38 expression on tetramer + β7 + T cells and did not find a significant difference between the one- and three-day challenges.
CONCLUSIONS
The optimal time points for monitoring therapy response in CeD after a three-day oral gluten challenge is four hours for plasma IL-2 or six to eight days for the frequency of tetramer + β7 + T cells, but both these parameters involved large interindividual differences. In contrast, CD38 expression on tetramer + β7 + T cells increased uniformly and irrespectively of the length of gluten challenge, suggesting that this parameter is more suited for monitoring drug efficacy in clinical trials for CeD.
背景
人们正在努力为乳糜泻（CeD）寻找新的治疗方法，这是一种由麸质引起的小肠慢性疾病。在乳糜泻患者摄入麸质后，血液中的白细胞介素-2（IL-2）和麸质特异性 CD4+T 细胞分别在 4 小时和 6 天后增加。这些反应是乳糜泻特有的，在对照组中不会出现。我们旨在评估不同的标志物，这些标志物反映了对麸质暴露的回忆反应，可用于监测治疗效果。
方法
接受无麸质饮食的乳糜泻患者接受了为期一天（ = 6）或三天（ = 7）的口服麸质挑战。我们在基线和第 8 天之间的多个时间点采集血液样本，并使用 HLA-DQ:gluten 四聚体监测麸质特异性 CD4+T 细胞的频率和 CD38 表达。我们在第一次摄入麸质后 4 小时测量血浆中 IL-2 的浓度。
结果
在一天和三天的麸质挑战后，肠归巢、四聚体结合、CD4+效应记忆 T（tetramer+β7+T）细胞的频率和测量的 IL-2 浓度在第一次摄入麸质后显著增加，但个体间差异很大。在第 6 天至第 8 天之间，tetramer+β7+T 细胞的频率达到平台期，且在一天的挑战后更低。我们观察到 tetramer+β7+T 细胞上 CD38 表达的一致增加，并且在一天和三天的挑战之间未发现显著差异。
结论
在三天口服麸质挑战后监测乳糜泻治疗反应的最佳时间点是四聚体+β7+T 细胞频率的 4 小时，或 IL-2 浓度的 6 至 8 天，但这两个参数都涉及很大的个体间差异。相比之下，四聚体+β7+T 细胞上的 CD38 表达均匀增加，与麸质挑战的长度无关，表明该参数更适合在乳糜泻的临床试验中监测药物疗效。
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