Holler, Ernst and Rogler, Gerhard and Herfarth, Hans and Brenmoehl, Julia and Wild, Peter Johannes and Hahn, Joachim and Eissner, Guenther and Schoelmerich, Juergen and Andreesen, Reinhard (2004) Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. BLOOD, 104 (3). pp. 889-894. ISSN 0006-4971,
Full text not available from this repository. (Request a copy)Abstract
Single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene resulting in a diminished nuclear factor-kappaB (NF-kappaB) response to bacterial cell wall products have been associated with an increased incidence of Crohn disease. To assess a possible contribution of NOD2/CARD15 mutations to graft-versus-host disease (GvHD) and complications following allogeneic stem cell transplantation, we retrospectively typed DNA from donor/recipient pairs in 169 consecutive patients receiving transplants from related or unrelated donors. Mutated alleles were observed in 21% of patients and in 14% of donors. Cumulative incidence of 1-year, transplant-related mortality rose from 20% in donor/recipient pairs without mutated SNPs to 49% in pairs with recipient mutations (P = .03) and 59% in pairs with donor mutations (P < .005), and was highest in 12 pairs with mutated alleles in both donor and recipients (83%; P < .001). Similar associations were observed for severe overall and severe gastrointestinal GvHD. The impact of NOD2/CARD15 mutations was more prominent for HLA-identical sibling transplantations but was also observed in unrelated donor transplantation. Mutations proved to be independent risk factors for transplant-related mortality. Our findings indicate a major role of monocyte/macrophage dysfunction in the pathophysiology of GvHD and strongly suggest a future risk-assessment or even donor selection through NOD2/CARD15 typing.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CROHNS-DISEASE; EPITHELIAL-CELLS; NOD2 VARIANTS; GRAFT; SUSCEPTIBILITY; CARD15; LIPOPOLYSACCHARIDE; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2021 09:36 |
| Last Modified: | 05 Jul 2021 09:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37365 |
Actions (login required)
 |
View Item |
