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; Wolff, Daniel; Hertenstein, Bernd; Greinix, Hildegard T.; Brenmoehl, Julia; Schulz, Christian; Dickinson, Anne M.; Hahn, Joachim; Rogler, Gerhard; Andreesen, Reinhard; Holler, Ernst

doi:10.1016/j.bbmt.2007.09.009

« Previous Next »Biology of Blood and Marrow Transplantation
Volume 14, Issue 1 , Pages 67-74, January 2008

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

Gerhard C. Hildebrandt
- Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany
- Correspondence and reprint requests: Gerhard C Hildebrandt, Department of Hematology and Oncology, University of Regensburg Medical School, Franz-Josef-Strauß Allee 11, D-93053 Regensburg, Germany; Tel: +49-941-944-5589, Fax: +49-941-944-5511.
Miguell Granell
- Department of Hematology, Faculty of Medicine, University of Barcelona, Barcelona, Spain
Alvaro Urbano-Ispizua
- Department of Hematology, Faculty of Medicine, University of Barcelona, Barcelona, Spain
Daniel Wolff
- Department of Hematology and Oncology, University of Rostock Medical School, Rostock, Germany
Bernd Hertenstein
- Department of Hematology, Hannover Medical University, Hannover, Germany
Hildegard T. Greinix
- Department of Internal Medicine I, Vienna Medical University, Vienna, Austria
Julia Brenmoehl
- Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany
Christian Schulz
- Department of Pulmonology, University of Regensburg Medical School, Regensburg, Germany
Anne M. Dickinson
- School of Clinical and Laboratory Sciences, University of Newcastle, Newcastle, United Kingdom
Joachim Hahn
- Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany
Gerhard Rogler
- Department of Gastroenterology, University of Regensburg Medical School, Regensburg, Germany
Reinhard Andreesen
- Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany
Ernst Holler
- Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany

Received 29 April 2007; accepted 20 September 2007.

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.