TY - JOUR
T1 - Recipient NOD2/CARD15 Variants
T2 - A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation
AU - Hildebrandt, Gerhard C.
AU - Granell, Miguell
AU - Urbano-Ispizua, Alvaro
AU - Wolff, Daniel
AU - Hertenstein, Bernd
AU - Greinix, Hildegard T.
AU - Brenmoehl, Julia
AU - Schulz, Christian
AU - Dickinson, Anne M.
AU - Hahn, Joachim
AU - Rogler, Gerhard
AU - Andreesen, Reinhard
AU - Holler, Ernst
N1 - Funding Information:
This work was partially supported by European Community grant QLRT-CT-2001-01936 (“Transeurope”).
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Bronchiolitis obliterans
KW - Chronic GVHD
KW - NOD2
KW - Stem cell transplantation
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U2 - 10.1016/j.bbmt.2007.09.009
DO - 10.1016/j.bbmt.2007.09.009
M3 - Article
C2 - 18158963
AN - SCOPUS:37349073107
SN - 1083-8791
VL - 14
SP - 67
EP - 74
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 1
ER -