Cellular Stress Reactions During Graft-versus-host Disease

Completed

• Conditions: Graft Versus Host Disease; Graft Vs Host Disease
• Interventions: Diagnostic Test: Immunohistochemistry on intestinal biopsies

• Registration Number: NCT04558788
• Lead Sponsor: University of Freiburg

Brief Summary

This study has the aim to analyze intestinal expression of cellular stress molecules in patients with intestinal GVHD. Patients with colitis and patients without intestinal inflammation will serve as controls.

Detailed Description

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Acute GVHD results from a complex multi-step crosstalk between extensive epithelial tissue damage in the patient and activation of the allo-reactive immune system transferred with the donor graft. The conditioning treatment prior to allo-HCT creates an inflamed microenvironment with high concentrations of pathogen-associated and danger-associated molecular patterns (PAMPs and DAMPs) as well as pro-inflammatory cytokines. This inflammation is perpetuated by activation of myeloid immune cells and recruitment of allo-reactive T cells to the intestine. Enterocytes are subjected to cellular stress and undergo apoptosis. As a result, patients can develop high-voluminous diarrhea, dehydration, intestinal bleeding, hypalbuminemia, and generalized infections.

In this study, the investigators aim to analyze the expression of molecules related to different types of cellular stress in the intestine of patients with acute GVHD. The hypothesis is that some stress-related markers would be upregulated during GVHD. The results will be valuable to study the role of cellular stress reactions during acute GVHD pathogenesis or as potential biomarkers for disease activity.

Study Timeline

• Study Start: 2018-11-01
• Study First Submitted: 2020-09-16
• Study First Submitted QC: 2020-09-16
• Study First Posted: 2020-09-22
• Primary Completion: 2021-12-31
• Study Completion: 2021-12-31
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Age >18 years intestinal biopsy depending on cohort: healthy intestinal tissue, colitis or GVHD

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Uninflamed intestine	Immunohistochemistry on intestinal biopsies	Patients who underwent diagnostic endoscopy and received a diagnosis of no intestinal inflammation
Acute GVHD	Immunohistochemistry on intestinal biopsies	Patients with acute gastrointestinal (GI) GVHD
Colitis	Immunohistochemistry on intestinal biopsies	Patients with active colitis

Primary Outcome Measures

Name	Time	Method
Immunohistochemical staining	1 year	Immunohistochemical staining

Trial Locations

Locations (1)

Medical Center University of Freiburg; 🇩🇪 Freiburg, Baden-Württemberg, Germany