SEARCH:   Advanced

Blood, 1 August 2004, Vol. 104, No. 3, pp. 889-894. Prepublished online as a Blood First Edition Paper on April 15, 2004; DOI 10.1182/blood-2003-10-3543. This Article Full Text (PDF) All Versions of this Article: 2003-10-3543v1 104/3/889    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Holler, E. Articles by Andreesen, R. Search for Related Content PubMed PubMed Citation Articles by Holler, E. Articles by Andreesen, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 16, 2003 Accepted April 2, 2004 Both, donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation Ernst Holler*, Gerhard Rogler, Hans Herfarth, Julia Brenmoehl, Peter Johannes Wild, Joachim Hahn, Guenther Eissner, Juergen Schoelmerich, and Reinhard Andreesen Division of Hematology/Oncology, University of Regensburg, Regensburg, Germany Department of Internal Medicine I, University of Regensburg, Regensburg, Germany Institute of Pathology, University of Regensburg, Regensburg, Germany * Corresponding author; email: ernst.holler{at}klinik.uni-regensburg.de. Single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene resulting in a diminished NF-kB response to bacterial cell wall products have been associated with an increased incidence of Crohns disease. To assess a possible contribution of NOD2/CARD15 mutations to GvHD and complications following allogeneic stem cell transplantation, we retrospectively typed DNA from donor/recipient pairs in 169 consecutive patients receiving related or unrelated transplants. Mutated alleles were observed in 21% of patients and in 14% of donors: Cumulative incidence of 1 yr transplant related mortality rose from 20% in donor/recipient pairs without mutated SNPs to 49 % in pairs with recipient mutations (p 0.03), 59% in pairs with donor mutations (p < 0.005) and was highest in 12 pairs with mutated alleles in both, donor and recipients (83%, p< 0.001). Similar associations were observed for severe overall and severe gastrointestinal GvHD. The impact of NOD2/CARD15 mutations was more prominent for HLA-identical sibling transplants but was also observed in unrelated donor transplantation. Mutations proved to be independent risk factors for transplant related mortality. Our findings indicate a major role of a dysregulated antibacterial response by epithelial cells and monocytes in the pathophysiology of GvHD and strongly suggest a future risk assessment through NOD2/CARD15 typing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L. Espinoza, A. Takami, M. Onizuka, H. Sao, H. Akiyama, K. Miyamura, S. Okamoto, M. Inoue, Y. Kanda, S. Ohtake, et al. NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies Haematologica, October 1, 2009; 94(10): 1427 - 1434. [Abstract] [Full Text] [PDF] O. Penack, O. M. Smith, A. Cunningham-Bussel, X. Liu, U. Rao, N. Yim, I.-K. Na, A. M. Holland, A. Ghosh, S. X. Lu, et al. NOD2 regulates hematopoietic cell function during graft-versus-host disease J. Exp. Med., September 28, 2009; 206(10): 2101 - 2110. [Abstract] [Full Text] [PDF] M. Granell, A. Urbano-Ispizua, A. Pons, J. I. Arostegui, B. Gel, A. Navarro, S. Jansa, R. Artells, A. Gaya, C. Talarn, et al. Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation Blood, November 15, 2008; 112(10): 4337 - 4342. [Abstract] [Full Text] [PDF] Y.-G. Kim, J.-H. Park, S. Daignault, K. Fukase, and G. Nunez Cross-Tolerization between Nod1 and Nod2 Signaling Results in Reduced Refractoriness to Bacterial Infection in Nod2-Deficient Macrophages J. Immunol., September 15, 2008; 181(6): 4340 - 4346. [Abstract] [Full Text] [PDF] H. Hauser, O. Zach, O. Krieger, H. Kasparu, J. Koenig, M. Girschikofsky, R. Oberbauer, and D. Lutz A single nucleotide polymorphism at chromosome 2q21.3 (LCT -13910C>T) associates with clinical outcome after allogeneic hematopoietic stem cell transplantation Blood, September 1, 2008; 112(5): 2156 - 2159. [Abstract] [Full Text] [PDF] T Fishbein, G Novitskiy, L Mishra, C Matsumoto, S Kaufman, S Goyal, K Shetty, L Johnson, A Lu, A Wang, et al. NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine Gut, March 1, 2008; 57(3): 323 - 330. [Abstract] [Full Text] [PDF] E. Holler, J. Hahn, R. Andreesen, G. Rogler, J. Brenmoehl, H. Greinix, A. M. Dickinson, G. Socie, D. Wolff, and J. Finke NOD2/CARD15 Polymorphisms in Allogeneic Stem-Cell Transplantation From Unrelated Donors: T Depletion Matters J. Clin. Oncol., January 10, 2008; 26(2): 338 - 339. [Full Text] [PDF] N. P. Mayor, B. E. Shaw, D. A. Hughes, H. Maldonado-Torres, J. A. Madrigal, S. Keshav, and S. G.E. Marsh In Reply J. Clin. Oncol., January 10, 2008; 26(2): 339 - 339. [Full Text] [PDF] N. P. Mayor, B. E. Shaw, D. A. Hughes, H. Maldonado-Torres, J. A. Madrigal, S. Keshav, and S. G.E. Marsh Single Nucleotide Polymorphisms in the NOD2/CARD15 Gene Are Associated With an Increased Risk of Relapse and Death for Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation With Unrelated Donors J. Clin. Oncol., September 20, 2007; 25(27): 4262 - 4269. [Abstract] [Full Text] [PDF] M Devetten and J. Armitage Hematopoietic cell transplantation: progress and obstacles Ann. Onc., September 1, 2007; 18(9): 1450 - 1456. [Abstract] [Full Text] [PDF] M. Ditschkowski, A. H. Elmaagacli, R. Trenschel, R. Peceny, M. Koldehoff, C. Schulte, and D. W. Beelen T-cell depletion prevents from bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia after allogeneic hematopoietic stem cell transplantation with related donors Haematologica, April 1, 2007; 92(4): 558 - 561. [Abstract] [Full Text] [PDF] E. Holler, G. Rogler, J. Brenmoehl, J. Hahn, H. Herfarth, H. Greinix, A. M. Dickinson, G. Socie, D. Wolff, G. Fischer, et al. Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination Blood, May 15, 2006; 107(10): 4189 - 4193. [Abstract] [Full Text] [PDF] E. A. Copelan Hematopoietic stem-cell transplantation. N. Engl. J. Med., April 27, 2006; 354(17): 1813 - 1826. [Full Text] [PDF] Z. F. M. Vasconcelos, B. M. dos Santos, J. Farache, T. S. S. Palmeira, R. B. Areal, J. M. T. Cunha, M. A. Barcinski, and A. Bonomo G-CSF-treated granulocytes inhibit acute graft-versus-host disease Blood, March 1, 2006; 107(5): 2192 - 2199. [Abstract] [Full Text] [PDF] M. Mohty, D. Blaise, C. Faucher, N. Vey, R. Bouabdallah, A.-M. Stoppa, F. Viret, G. Gravis, D. Olive, and B. Gaugler Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation Blood, December 15, 2005; 106(13): 4407 - 4411. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020