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Bone Marrow Transplantation (2008) 41, 961964 & 2008 Nature Publishing Group All rights reserved 0268-3369/08 $30.00
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ORIGINAL ARTICLE
No impact of NOD2/CARD15 on outcome after SCT
D Saira1,2, M Uzunel2, M Remberger2, O Ringdn1,2 and J Mattsson1,2
1Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden and 2Institution of Laboratory medicine, Department of Clinical Immunology, Karolinska Institutet, Stockholm, Sweden
Recent studies have pointed towards an association between certain single nucleotide polymorphisms (SNPs) in the NOD2/CARD15 gene, and negative outcome of Allo-SCT. In this study, 198 patients and their corresponding donors were analyzed retrospectively for the occurrence of NOD2/CARD15 mutations to evaluate the impact on clinical results after Allo-SCT. In all, 7.6% of the patients and 11% of the donors were heterozygous for one of three SNPs 8, 12 or 13. Contrary to earlier ndings, we found no signicant impact on incidence of acute GVHD or TRM following Allo-SCT. These differences in results could be due to a lower mutation frequency in the studied population and/or a lower overall incidence of severe GVHD. On the basis of these ndings we conclude that a consideration to NOD2/CARD15 mutation status is not pertinent when selecting a donor for Allo-SCT at our centre. Bone Marrow Transplantation (2008) 41, 961964; doi:http://dx.doi.org/10.1038/bmt.2008.9
Web End =10.1038/bmt.2008.9 ; published online 3 March 2008 Keywords: SCT; GVHD; NOD2; TRM
Introduction NOD2/CARD15 was initially identied as the rst gene linked to increased susceptibility for Crohns disease.1,2 It is
expressed in paneth cells in the intestinal mucosa and myeloid-derived cells such as monocytes/macrophages, neutrophils and DCs. It encodes for a cytoplasmic protein that has been shown to function as a sensor for the cell wall component muramyl dipeptide, which is present in both gram-positive and gram-negative bacteria. NOD2/CARD15 partakes in activation of the rst-line epithelial defence in the intestine, and regulation of inammatory response through intracellular pathways involving nuclear factor kB and IkB kinase.3
Recent studies have pointed towards an association between certain single nucleotide polymorphisms (SNPs) in
the NOD2/CARD15 gene, and an increased incidence of severe acute GVHD, intestinal GVHD and TRM following Allo-SCT.46 This increased risk was correlated with occurrence of the gene variants in recipients, as well as in donors, even though the results have been...