Polymorphisms Within Epithelial Receptors: NOD2/CARD15

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.