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Completed

NCT Number: NCT05733663

TCRγδ+ Cells After Gluten-free Diet: A Biomarker for Coeliac Disease?

Coeliac disease (CD) is a systemic process of autoimmune nature related to the existence of a permanent intolerance to gluten and manifests itself in genetically susceptible individuals. It has a global prevalence of 0.5-1.5%. The diagnosis of CD should be made in patients following a normal gluten-containing diet and is based on coeliac serology and histopathological changes of the small intestinal mucosa. However, nowadays many patients come to their doctor to rule out CD after having started a gluten-free diet (GFD) with improvement of symptoms. In this scenario, making the diagnosis of CD remains a challenge, as it must be considered that most CD-associated changes revert after gluten withdrawal.

An essential finding of CD is the increased number in total intraepithelial lymphocytes (IEL) in the duodenal mucosa, later characterized by an expansion of γδ+ and CD8+ IEL coupled to a decrease in CD3- IEL. An accurate quantification of the γδ+ subset became possible with the introduction of flow cytometry. In 2002, Spanish investigators proposed a diagnostic algorithm for paediatric CD that included the combined use of a high percentage of γδ+ and a low percentage of CD3- IEL, which was termed the coeliac lymphogram, which has been shown to be very accurate for the diagnosis of CD. Thus, the use of flow cytometric phenotyping of IEL may strengthen the diagnosis of CD when it is not straightforward.

This study will provide information about the potential usefulness of T-cell flow cytometric coeliac patterns as CD biomarkers to confirm the diagnosis of CD in patients who have already started a GFD. These results may help to make decisions in specific situations of routine clinical practice, avoiding bothersome gluten reintroduction and delays in diagnosis.

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Key information

Conditions

Celiac Disease Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutritional and Metabolic Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital Universitari Mutua Terrassa

Terrassa, Barcelona, 08221, Spain

About this study

Hypothesis:

The increase in the TCRγδ+ subset appears to be permanent despite a GFD, which opens up the possibility of using it as a diagnostic tool in patients following a GFD, without the need to undergo gluten challenge. Several studies have focused on this aspect with promising results, but the studies have been performed on small samples of patients, and follow-up time after a GFD has not always been described or only changes in mean values before versus after the diet have been reported.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Paediatric or adult patients diagnosed with CD and started on a strict GFD
  • Patients with a follow-up intestinal biopsy to assess histological remission at least 1-year after starting the GFD
  • Assessment of the intraepithelial lymphogram at both baseline and follow-up
  • Presence of increased TCRγδ+ cells at baseline.

Exclusion criteria

  • Refusal of the patient to participate in the registry.
  • Pregnancy and severe comorbidities (heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc).
  • Patients with intake of NSAIDs or Olmesartan.
  • Patients with Crohn's disease, autoimmune disease associated enteropathy, collagenous sprue, microscopic colitis, lymphocytic enteritis due to intestinal parasitosis or Helicobacter pylori infection, other enteropathies.
  • Selective IgA deficiency.

Treatment and study plan

Endoscopic procedure with duodenal biopsy

Diagnostic Test
  • In all patients the investigators will analyse coeliac serology, DQ-genotype, and results of two duodenal biopsy sampling (one at diagnosis before starting the GFD and another sampling during follow-up with GFD) for assessment of both histopathology and intraepithelial lymphocyte subpopulations by T-cell flow cytometry. In addition, clinical, serological, and histological response to GFD will be evaluated.
  • T-cell flow cytometry assay is performed as previously described by our group in previous studies. In all patients, an additional duodenal biopsy sample is taken from the second-third portion of the duodenum at the same endoscopic procedure that for histopathology. The normal cut-off values for the IEL cytometric pattern in our laboratory are CD3+TCRγδ+ IEL ≤8.5% (≤mean + 2SD) and CD3- IEL ≥10% (10th percentile). The cut-offs define four intraepithelial lymphogram patterns: normal, isolated decrease in CD3- cells, isolated increase in TCRγδ+ cells, and the coeliac lymphogram.

Primary outcomes

  1. Percentage of long-term persistence of both the coeliac lymphogram (increase in TCRγδ+ and decrease in CD3- cells) and the isolated increase in TCRγδ+ cells measured by T-cell flow cytometry in CD patients after starting a GFD.

    Time frame: 1 year

    Lymphocyte subpopulations (TCRγδ+ and CD3- cells) are measured by flow cytometry.

Secondary outcomes

  1. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to baseline histology (measured by Marsh Classification: 0, 1, 2 or 3)

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

  2. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to age group (measured by years).

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

  3. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to gender (classified according to male or female sex).

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

  4. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to coeliac serology (measured by presence or absence of anti-transglutaminase antibodies).

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

  5. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to DQ-genotype (measured by presence or absence of HLA-DQ2.5).

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

  6. Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to follow-up time (measured by years).

    Time frame: 1 year

    To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.

Other outcomes

  1. Frequency of persisting CD changes despite a GFD (i.e., positive CD serology, persistent villous atrophy) at the time of follow-up biopsy and compare them with the frequency of a persistent increase in γδ+ subset.

    Time frame: 1 year

Sponsors and collaborators

Lead sponsor

Hospital Mutua de Terrassa

Other

Registry information

Official study title

Persistent Increase in the Intestinal γδ+ T-cell Subset: A Potential Biomarker of Coeliac Disease in Patients Started on a Gluten-free Diet

Acronym: GFDL

Important dates

Study start
2013
Primary completion
2020
Study completion
2020
First posted
Feb 17, 2023
Registry last updated
Apr 6, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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