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Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease
- Publication Year :
- 2010
- Publisher :
- Wiley-Blackwell, 2010.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....967efae4e4765e39e4ac3157ac089f65
- Full Text :
- https://doi.org/10.5167/uzh-32459