Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation

Gerhard C. Hildebrandt; Miguell Granell; Alvaro Urbano-Ispizua; Daniel Wolff; Bernd Hertenstein; Hildegard T. Greinix; Julia Brenmoehl; Christian Schulz; Anne M. Dickinson; Joachim Hahn; Gerhard Rogler; Reinhard Andreesen; Ernst Holler

doi:10.1016/j.bbmt.2007.09.009

Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation

Gerhard C. Hildebrandt, Miguell Granell, Alvaro Urbano-Ispizua, Daniel Wolff, Bernd Hertenstein, Hildegard T. Greinix, Julia Brenmoehl, Christian Schulz, Anne M. Dickinson, Joachim Hahn, Gerhard Rogler, Reinhard Andreesen, Ernst Holler

Internal Medicine

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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.

Original language	English
Pages (from-to)	67-74
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.bbmt.2007.09.009
State	Published - Jan 2008

Bibliographical note

Funding Information:
This work was partially supported by European Community grant QLRT-CT-2001-01936 (“Transeurope”).

Funding

This work was partially supported by European Community grant QLRT-CT-2001-01936 (“Transeurope”).

Funders	Funder number
European Community	QLRT-CT-2001-01936

Keywords

Bronchiolitis obliterans
Chronic GVHD
NOD2
Stem cell transplantation

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2007.09.009

Cite this

Hildebrandt, G. C., Granell, M., Urbano-Ispizua, A., Wolff, D., Hertenstein, B., Greinix, H. T., Brenmoehl, J., Schulz, C., Dickinson, A. M., Hahn, J., Rogler, G., Andreesen, R., & Holler, E. (2008). Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 14(1), 67-74. https://doi.org/10.1016/j.bbmt.2007.09.009

@article{412e905008b64cb297bdb94e30453108,

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.",

keywords = "Bronchiolitis obliterans, Chronic GVHD, NOD2, Stem cell transplantation",

author = "Hildebrandt, {Gerhard C.} and Miguell Granell and Alvaro Urbano-Ispizua and Daniel Wolff and Bernd Hertenstein and Greinix, {Hildegard T.} and Julia Brenmoehl and Christian Schulz and Dickinson, {Anne M.} and Joachim Hahn and Gerhard Rogler and Reinhard Andreesen and Ernst Holler",

note = "Funding Information: This work was partially supported by European Community grant QLRT-CT-2001-01936 (“Transeurope”).",

year = "2008",

month = jan,

doi = "10.1016/j.bbmt.2007.09.009",

language = "English",

volume = "14",

pages = "67--74",

number = "1",

}

Hildebrandt, GC, Granell, M, Urbano-Ispizua, A, Wolff, D, Hertenstein, B, Greinix, HT, Brenmoehl, J, Schulz, C, Dickinson, AM, Hahn, J, Rogler, G, Andreesen, R & Holler, E 2008, 'Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 14, no. 1, pp. 67-74. https://doi.org/10.1016/j.bbmt.2007.09.009

Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation. / Hildebrandt, Gerhard C.; Granell, Miguell; Urbano-Ispizua, Alvaro et al.
In: Biology of Blood and Marrow Transplantation, Vol. 14, No. 1, 01.2008, p. 67-74.

Research output: Contribution to journal › Article › peer-review

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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M3 - Article

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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 -

Recipient NOD2/CARD15 Variants: A Novel Independent Risk Factor for the Development of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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