CD38 expression on gluten-specific T cells is a robust marker of gluten re-exposure in coeliac disease.

ABSTRACT

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- (n = 6) or three-day (n = 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-DQgluten 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 + ß7 + TEM) 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 + ß7 + TEM plateaued between days 6 and 8 and was lower after the one-day challenge. We observed a consistent increase in CD38 expression on tetramer + ß7 + TEM 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 + ß7 + TEM cells, but both these parameters involved large interindividual differences. In contrast, CD38 expression on tetramer + ß7 + TEM 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.