Abstract
Genetic risk assessment in the setting of allogeneic stem cell transplantation is one of the major goals to optimise future prophylaxis and treatment of patients: our group has focused on analysis of single-nucleotide polymorphisms (SNPs) within the intracytoplasmatic receptor NOD2/CARD15, which recognizes the bacterial cell wall compound muramyl-dipeptide and induces nuclear factor-KB-mediated inflammation. By performing TaqMan PCR of the three major SNPs also identified as risk factors in Crohn’s disease in donors and recipients, we were able to demonstrate a major association of NOD2/CARD15 SNPs with the occurrence of severe graft-vs-host disease and resulting treatment-related mortality following human leukocyte antigen-identical sibling transplantation. Although these data need confirmation in further prospective trials, this association may not only be used for risk assessment but also point to a major pathophysiological interaction of dysregulated activation of the innate immune system and specific alloreaction.
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References
Dickinson, A. M., Middleton, P. G., Rocha, V., Gluckman, E., and Holler, E. (2004) Genetic polymorphisms predicting the outcome of bone marrow transplants. Br. J. Haematol. 127, 479–490.
Ferrara, J. L. (2002) Cellular and cytokine effectors of acute graft versus host disease. Int. J. Hematol. 76, 195–198.
Hugot, J. P., Chamaillard, M., Zouali, H., et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411, 599–603.
Ogura, Y., Bonen, D. K., Inohara, N., et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411, 603–606.
Hampe, J., Grebe, J., Nikolaus, S., et al. (2002) Association of NOD2 (CARD 15) genotype with clinical course of Crohn’s disease: a cohort study. Lancet 359, 1661–1665.
Holler, E., Rogler, G., Herfarth, H., et al. (2004) Both donor and recipient NOD2/CARD 15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 104 889–894.
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© 2007 Humana Press Inc.
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Brenmoehl, J., Holler, E., Rogler, G. (2007). Polymorphisms Within Epithelial Receptors. In: Beksac, M. (eds) Bone Marrow and Stem Cell Transplantation. Methods in Molecular Medicine, vol 134. Humana Press. https://doi.org/10.1007/978-1-59745-223-6_9
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DOI: https://doi.org/10.1007/978-1-59745-223-6_9
Publisher Name: Humana Press
Print ISBN: 978-1-58829-595-8
Online ISBN: 978-1-59745-223-6
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