title: Recipient NOD2/CARD15 variants: a novel independent risk factor for the development of bronchiolitis obliterans after allogeneic stem cell transplantation.
abstract: Bronchiolitis obliterans (BO) is a serious complication after allogeneic stem cell transplantation. We hypothesized that single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene (=NOD2/CARD15 variants) contribute to changes in host defense and subsequent alloreaction, leading to BO. We analyzed 427 donor-recipient pairs for the association of NOD2/CARD15 variants (SNP8 [Arg702Trp], SNP12 [Gly908Arg], and SNP13 [Leu1007fsinsC]) with BO occurrence. Overall, 11 patients (2.6%) developed BO. The cumulative incidence of BO rose from 1.3% in donor-recipient pairs without mutation to 18.7% in pairs with donor or recipient NOD2/CARD15 variants (P < .001). Recipient NOD2/CARD15 variants alone led to BO in 22.3% (P < .001), whereas donor variants alone associated with BO in 13.2% (P = .04). Multivariate analysis proved recipient but not donor NOD2/CARD15 variants to be a novel independent risk factor for BO development, and NOD2/CARD15 typing may help identify patients at increased risk for BO.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany. gerhard.hildebrandt@klinik.uni-regensburg.de
authors.forename: Gerhard C
authors.initials: GC
authors.lastname: Hildebrandt
authors.forename: Miguell
authors.initials: M
authors.lastname: Granell
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006086:Graft vs Host Disease / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein