Clinical trial NCT04522843: Analysis of Intestinal Defensin Expression in Acute GVHD
Official title: Analysis of Intestinal Defensin Expression in Patients With Acute Graft-versus-Host Disease (GVHD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: GVHD,Acute
Ulcerative Colitis
Morbus Crohn
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients who underwent diagnostic endoscopy

Brief summary: This study has the aim to analyze intestinal expression of endogenous antimicrobial peptides in patients with acute GVHD. The expression will be compared to intestinal expression of defensins in patients with colitis and patients without intestinal inflammation.

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 is characterized by complex deficiencies of the mucosal antimicrobial barrier and intestinal dysbiosis, which contribute to disease pathogenesis. Defensins are endogenous epithelial cell-derived antimicrobial peptides, which can protect epithelial barrier integrity, shape the intestinal microbiota composition and contribute to host immunoregulation. Deregulated expression of defensins has been reported in patients with colitis, including Chron's Disease and ulcerative colitis.

In this study, the investigators aim to analyze the expression of defensins in the intestine of patients with acute GVHD to study whether it is deregulated. The results will be valuable to study the role of defensins during acute GVHD pathogenesis or as potential biomarkers for disease activity.

Eligibility criteria: Inclusion Criteria:

* age ≥ 18 years
* diagnostic endoscopy was performed
* diagnosis results available
* written informed consent
* ability to understand the nature of the study and the study related procedures and to comply with them

Exclusion Criteria:

* age \< 18 years
* gastrointestinal cancer
* lack of informed consent

Primary outcomes:
measure: Defensin Expression (mRNA)
timeFrame: 3 years
measure: Defensin Expression (peptide)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Medical Center University of Freiburg
state: Baden-Württemberg
Study officials:
affiliation: Medical Center University of Freiburg
name: Robert Zeiser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wehkamp J, Fellermann K, Herrlinger KR, Baxmann S, Schmidt K, Schwind B, Duchrow M, Wohlschlager C, Feller AC, Stange EF. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002 Jul;14(7):745-52. doi: 10.1097/00042737-200207000-00006.
citation: Kohler N, Zeiser R. Intestinal Microbiota Influence Immune Tolerance Post Allogeneic Hematopoietic Cell Transplantation and Intestinal GVHD. Front Immunol. 2019 Jan 17;9:3179. doi: 10.3389/fimmu.2018.03179. eCollection 2018.
citation: Ruckert T, Andrieux G, Boerries M, Hanke-Muller K, Woessner NM, Doetsch S, Schell C, Aumann K, Kolter J, Schmitt-Graeff A, Schiff M, Braun LM, Haring E, Kissel S, Siranosian BA, Bhatt AS, Nordkild P, Wehkamp J, Jensen BAH, Minguet S, Duyster J, Zeiser R, Kohler N. Human beta-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling. Sci Transl Med. 2022 Dec 21;14(676):eabp9675. doi: 10.1126/scitranslmed.abp9675. Epub 2022 Dec 21.