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

共 49 条

[1] NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of inflammatory bowel disease [J].

Aldhous, MC ;

Nimmo, ER ;

Satsangi, J .

GUT, 2003, 52 (11) :1533-1535

[2] Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15 [J].

Becker, Mara L. ;

Martin, Tammy M. ;

Doyle, Trudy M. ;

Rose, Carlos D. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (04) :1292-1294

[3]

Beinert T, 1996, Eur J Med Res, V1, P343

[4] Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon [J].

Berrebi, D ;

Maudinas, R ;

Hugot, JP ;

Chamaillard, M ;

Chareyre, F ;

De Lagausie, P ;

Yang, C ;

Desreumaux, P ;

Giovannini, M ;

Cézard, JP ;

Zouali, H ;

Emilie, D ;

Peuchmaur, M .

GUT, 2003, 52 (06) :840-846

[5] IFNγ differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract [J].

Burman, Angela C. ;

Banovic, Tatjana ;

Kuns, Rachel D. ;

Clouston, Andrew D. ;

Stanley, Amanda C. ;

Morris, Edward S. ;

Rowe, Vanessa ;

Bofinger, Helen ;

Skoczylas, Renae ;

Raffelt, Neil ;

Fahy, Olivier ;

McColl, Shaun R. ;

Engwerda, Christian R. ;

McDonald, Kelli P. A. ;

Hill, Geoffrey R. .

BLOOD, 2007, 110 (03) :1064-1072

[6] Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation [J].

Chien, JW ;

Zhao, LP ;

Hansen, JA ;

Fan, WH ;

Parimon, T ;

Clark, JG .

BLOOD, 2006, 107 (05) :2200-2207

[7] Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation [J].

Chien, JW ;

Martin, PJ ;

Gooley, TA ;

Flowers, ME ;

Heckbert, SR ;

Nichols, WG ;

Clark, JG .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (02) :208-214

[8] OBSTRUCTIVE LUNG-DISEASE AFTER ALLOGENEIC MARROW TRANSPLANTATION - CLINICAL PRESENTATION AND COURSE [J].

CLARK, JG ;

CRAWFORD, SW ;

MADTES, DK ;

SULLIVAN, KM .

ANNALS OF INTERNAL MEDICINE, 1989, 111 (05) :368-376

[9] RISK-FACTORS FOR AIR-FLOW OBSTRUCTION IN RECIPIENTS OF BONE-MARROW TRANSPLANTS [J].

CLARK, JG ;

SCHWARTZ, DA ;

FLOURNOY, N ;

SULLIVAN, KM ;

CRAWFORD, SW ;

THOMAS, ED .

ANNALS OF INTERNAL MEDICINE, 1987, 107 (05) :648-656

[10] Airway goblet cells and respiratory epithelial injury in an animal model of obliterative airways disease (OAD) [J].

Dosanjh, A ;

Wan, B ;

Ikonen, T ;

Boeke, K ;

Morris, RE .

AMERICAN JOURNAL OF TRANSPLANTATION, 2001, 1 (04) :321-324

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