title: 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.
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.
authors.affiliation: Department of Haematology/Oncology, University of Regensburg, Regensburg, Germany. ernst.holler@klinik.uni-regensburg.de
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: G
authors.initials: G
authors.lastname: Rogler
authors.forename: J
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: J
authors.initials: J
authors.lastname: Hahn
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.forename: A M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: G
authors.initials: G
authors.lastname: Socie
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.forename: J
authors.initials: J
authors.lastname: Finke
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.forename: V
authors.initials: V
authors.lastname: Rocha
authors.forename: I
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: G
authors.initials: G
authors.lastname: Eissner
authors.forename: J
authors.initials: J
authors.lastname: Marienhagen
authors.forename: R
authors.initials: R
authors.lastname: Andreesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002985:Clinical Protocols; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007113:Immunity, Innate; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein