Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease
| Autor: | Juergen Schoelmerich, Petra Hoffmann, Florian Obermeier, Reinhard Andreesen, Joachim Hahn, Matthias Edinger, Gerhard Rogler, Frauke Bataille, K. Kosovac, Karin Landfried, Ernst Holler, Daniel Wolff, Inken Hilgendorf, J. Brenmoehl |
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| Přispěvatelé: | University of Zurich, Holler, E |
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Pathology medicine.medical_specialty Translational Studies Neutrophils Immunology Nod2 Signaling Adaptor Protein Graft vs Host Disease 610 Medicine & health Cell Count Biology CD8-Positive T-Lymphocytes Adrenal Cortex Hormones Cell Movement NOD2 medicine Immunology and Allergy Cytotoxic T cell Humans Transplantation Homologous Intestinal Mucosa 2403 Immunology Lamina propria Peripheral Blood Stem Cell Transplantation Innate immune system Mucous Membrane Polymorphism Genetic Forkhead Transcription Factors Middle Aged medicine.disease digestive system diseases Transplantation Intestines 10219 Clinic for Gastroenterology and Hepatology Graft-versus-host disease medicine.anatomical_structure 2723 Immunology and Allergy Stem cell CD8 Immunosuppressive Agents |
| DOI: | 10.5167/uzh-32459 |
| Popis: | Summary Nucleotide-binding oligomerization domain 2/caspase recruitment domain 15 (NOD2/CARD15) polymorphisms have been identified as risk factors of both Crohn's disease and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. However, the role of these receptors of innate immunity in the pathophysiology of gastrointestinal GVHD is still poorly defined. Immunohistological features of intestinal GVHD were analysed in gastrointestinal biopsies from 58 patients obtained at the time of first onset of intestinal symptoms. The observed changes were correlated with concomitant risk factors and the presence of polymorphisms within the pathogen recognition receptor gene NOD2/CARD15. Intestinal GVHD was associated with a stage-dependent decrease in CD4 T cell infiltrates and an increase in CD8 T cells in the lamina propria; CD8 infiltrates correlated with extent of apoptosis and consecutive epithelial proliferation. The presence of NOD2/CARD15 variants in the recipient was associated with a significant loss of CD4 T cells: in a semiquantitative analysis, the median CD4 score for patients with wild-type NOD2/CARD15 was 1·1 (range 3), but only 0·4 (range 2) for patients with variants (P = 0·002). This observation was independent from severity of GVHD in multivariate analyses and could not be explained by the loss of forkhead box P3+ T cells. Our results suggest a loss of protective CD4 T cells in intestinal GVHD which is enhanced further by the presence of NOD2/CARD15 variants. Our study might help to identify more selective therapeutic strategies in the future. |
| Databáze: | OpenAIRE |
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