K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway.
Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
United European Gastroenterol J. 2019 Dec;7(10):1337-1344. doi: 10.1177/2050640619874183. Epub 2019 Sep 7.
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.
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.
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.
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.
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。
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。
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。
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。
