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

NCT ID: NCT05733663

Last Updated: 2023-04-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 116 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-01
• Study Completion Date: 2020-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Celiac Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Adult patients diagnosed with coeliac disease

A group of paediatric or adult patients diagnosed with CD and started on a strict GFD, with baseline and a follow-up intestinal biopsy to assess histological and intraepithelial lymphogram at least 1-year after starting the GFD, and with increased γδ+ T-cells at baseline.

Endoscopic procedure with duodenal biopsy

Intervention Type: 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.

Interventions

Endoscopic procedure with duodenal biopsy

• 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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Mutua de Terrassa

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Esteve, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitari Mútua Terrassa

Locations

Hospital Universitari Mutua Terrassa

Terrassa, Barcelona, Spain

Countries

Spain

Other Identifiers

GFDL

Identifier Type: -

Identifier Source: org_study_id