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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Uninflamed intestine | Patients who underwent diagnostic endoscopy and received a diagnosis of no intestinal inflammation | ||
| Colitis | Patients with active colitis | ||
| Acute GVHD | Patients with acute gastrointestinal (GI) GVHD |
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| Measure | Description | Time Frame |
|---|---|---|
| Defensin Expression (mRNA) | Analysis of alpha-defensin and beta-defensin mRNA expression by realtime PCR (qRT-PCR) | 3 years |
| Defensin Expression (peptide) | Analysis of alpha-defensin and beta-defensin levels by immunohistochemistry | 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients who underwent diagnostic endoscopy
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| Name | Affiliation | Role |
|---|---|---|
| Robert Zeiser, Prof. Dr. | Medical Center University of Freiburg | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Center University of Freiburg | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12169983 | Background | 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. | |
| 30705680 |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| 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. |
| 36542690 | Result | 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. |
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |