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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
Author(s) -
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.
Publication year - 2008
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2008.00795.x
Subject(s) - single nucleotide polymorphism , innate immune system , immunology , nod2 , stem cell , transplantation , hematopoietic stem cell transplantation , biology , haematopoiesis , immunity , human leukocyte antigen , immune system , medicine , genetics , antigen , gene , genotype
Summary 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.