• Transplantation · Jan 2006

    Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation.

    • Ahmet H Elmaagacli, Michael Koldehoff, Heidrun Hindahl, Nina K Steckel, Rudolf Trenschel, Rudolf Peceny, Hellmut Ottinger, Peter-Michael Rath, Rudolf Stefan Ross, Michael Roggendorf, Hans Grosse-Wilde, and Dietrich W Beelen.
    • Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany. ahmet.elmaagacli@uni-essen.de
    • Transplantation. 2006 Jan 27;81(2):247-54.

    BackgroundNOD2 and TLR-4 genes belong to the innate immune system that detects invading pathogens through several pattern-recognition receptors. Here we analyzed 403 patients for NOD2 gene mutations and 307 patients for TLR-4 gene mutations (Thr399Ile) with their respective donors and correlated the results with the incidence of acute graft-versus-host disease (aGVHD), severe acute GVHD (saGVHD), the risk for transplant-related mortality (TRM), overall survival (OS) and incidence of infectious complications.MethodsWe performed a retrospective single-center study. Genotyping of TLR-4 and NOD2 were evaluated by real-time polymerase chain reaction.ResultsSurprisingly, we found a significant reduced incidence of aGVHD, saGVHD, and intestinal GVHD for patients with NOD2 gene mutations on the donor side with 50%, 0% and 2% compared to patients with the wild-type NOD2 gene with 65%, 17%, and 26%, respectively (P<0.02). However, the incidence of saGVHD increased in patients with NOD2 mutations on the patient and donor (P/D) side with 44% versus 17% compared to patients with the wild-type gene (P<0.03). TLR-4 gene mutations at P/D side had an increased risk for saGVHD with 42% versus 15% of patients with wild-type gene (P<0.04). OS, TRM, and incidence of infectious complications were not influenced by the mutated genes. Multivariate analysis confirmed that NOD2 gene mutations on the donor side had a reduced risk for saGVHD (P<0.001), whereas mutations of the NOD2 gene on P/D side had an increased risk for saGVHD (P<0.01) in our analysis.ConclusionsThese results suggest that NOD2 mutations have influence on the occurrence of acute GVHD after transplantation.

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