Recipient NOD2/CARD15 variants:: A novel independent risk factor for the development of bronchiolitis obliterans after allogeneic stem cell transplantation

被引：43

作者：

Hildebrandt, Gerhard C. ^{[1
]}

Granell, Miguell ^{[4
]}

Urbano-Lspizua, Alvaro ^{[4
]}

Wolff, Daniel ^{[5
]}

Hertenstein, Bernd ^{[6
]}

Greinix, Hildegard T. ^{[7
]}

Brenmoehl, Julia ^{[1
]}

Schulz, Christian ^{[2
]}

Dickinson, Anne M. ^{[8
,9
]}

Hahn, Joachim ^{[1
]}

Rogler, Gerhard ^{[3
]}

Andreesen, Reinhard ^{[1
]}

Holler, Ennst ^{[1
]}

机构：

[1] Univ Regensburg, Sch Med, Dept Hematol & Oncol, D-93053 Regensburg, Germany

[2] Univ Regensburg, Sch Med, Dept Pulmonol, D-93053 Regensburg, Germany

[3] Univ Regensburg, Sch Med, Dept Gastroenterol, D-93053 Regensburg, Germany

[4] Univ Barcelona, Fac Med, Dept Hematol, Barcelona 7, Spain

[5] Univ Rostock, Sch Med, Dept Hematol & Oncol, Rostock, Germany

[6] Hannover Med Sch, Dept Hematol, Hannover, Germany

[7] Vienna Med Univ, Dept Internal Med 1, Vienna, Austria

[8] Univ Newcastle, Sch Clin, Newcastle Upon Tyne, Tyne & Wear, England

[9] Univ Newcastle, Sci Labs, Newcastle Upon Tyne, Tyne & Wear, England

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2008年 / 14卷 / 01期

关键词：

bronchiolitis obliterans; chronic GVHD; NOD2; stem cell transplantation;

D O I：

10.1016/j.bbmt.2007.09.009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (c) 2008 American Society for Blood and Marrow Transplantation.

引用

页码：67 / 74

页数：8

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