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The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation


Holler, E; Rogler, G; Brenmoehl, J; Hahn, J; Greinix, H; Dickinson, A M; Socie, G; Wolff, D; Finke, J; Fischer, G; Jackson, G; Rocha, V; Hilgendorf, I; Eissner, G; Marienhagen, J; Andreesen, R (2008). The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation. International Journal of Immunogenetics, 35(4-5):381-384.

Abstract

Previous studies from our group indicated a role of SNPs within the innate immunity receptor NOD2/CARD15 as a risk factor for GvHD and treatment-related mortality allogeneic stem cell transplantation from HLA-identical siblings. We now extended these studies to assess the role of NOD2/CARD15 SNPs in 342 unrelated donor transplants. Overall, presence of any SNPs in patients or donor resulted in an increased risk of severe GvHD (25% in wildtype versus 38% in recipients and donors with variants, P= 0.01), which did not translate in increased mortality. When the analysis was broken down to individual SNPs, the presence of a SNP13 in the donor turned out to be the only highly significant risk factor (GvHD III/IV 22% wt, 42% SNP13 donor, P < 0.004; TRM 33% wt versus 59% SNP13 donor, P= 0.01; overall survival 49% wt versus 26% SNP13 donor, P= 0.007). This association was confirmed in multivariate analysis. Analysis of clinical risk factors suggested that this effect was most prominent in patients receiving any form of T cell depletion. Thus our observation indicates that the presence of a defect in innate immunity signalling in donor monocytes and possibly antigen presenting cells is most prominent in patients having additional T cell deficiency.

Previous studies from our group indicated a role of SNPs within the innate immunity receptor NOD2/CARD15 as a risk factor for GvHD and treatment-related mortality allogeneic stem cell transplantation from HLA-identical siblings. We now extended these studies to assess the role of NOD2/CARD15 SNPs in 342 unrelated donor transplants. Overall, presence of any SNPs in patients or donor resulted in an increased risk of severe GvHD (25% in wildtype versus 38% in recipients and donors with variants, P= 0.01), which did not translate in increased mortality. When the analysis was broken down to individual SNPs, the presence of a SNP13 in the donor turned out to be the only highly significant risk factor (GvHD III/IV 22% wt, 42% SNP13 donor, P < 0.004; TRM 33% wt versus 59% SNP13 donor, P= 0.01; overall survival 49% wt versus 26% SNP13 donor, P= 0.007). This association was confirmed in multivariate analysis. Analysis of clinical risk factors suggested that this effect was most prominent in patients receiving any form of T cell depletion. Thus our observation indicates that the presence of a defect in innate immunity signalling in donor monocytes and possibly antigen presenting cells is most prominent in patients having additional T cell deficiency.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:26 Mar 2010 08:09
Last Modified:05 Apr 2016 14:02
Publisher:Wiley-Blackwell
ISSN:1744-3121
Publisher DOI:10.1111/j.1744-313X.2008.00795.x
PubMed ID:18976442
Permanent URL: http://doi.org/10.5167/uzh-32549

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