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

United European Gastroenterol J. 2019 Dec;7(10):1337-1344. doi: 10.1177/2050640619874183. Epub 2019 Sep 7.

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-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 + 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 + β7 + 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 + β7 + 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 + β7 + TEM cells, but both these parameters involved large interindividual differences. In contrast, CD38 expression on tetramer + β7 + 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.

Trial registration: ClinicalTrials.gov NCT02464150.

Keywords: CD38; CD4; Coeliac disease; IL-2; T cells; activation marker; gluten; interleukin; kinetics; tetramers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / metabolism*
  • Adult
  • Aged
  • Antibodies / immunology
  • Biomarkers
  • Celiac Disease / diagnosis
  • Celiac Disease / etiology*
  • Celiac Disease / metabolism*
  • Cytokines / metabolism
  • Female
  • Gene Expression
  • Glutens / adverse effects
  • Glutens / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Protein Binding
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Young Adult

Substances

  • Antibodies
  • Biomarkers
  • Cytokines
  • HLA Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Glutens
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1

Associated data

  • ClinicalTrials.gov/NCT02464150