Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation

Abstract

BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene have been associated with the incidence and the severity of acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (SCT). We hypothesized that the clinical effect of SNP in NOD2/CARD15 might be different in patients submitted to T-cell-depleted allogeneic SCT, in which donor T cells, the main effectors of GVHD, are eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and chronic GVHD were not associated with either the donors' or recipients' NOD2/CARD15 variants. In contrast, these genetic variants were associated with a lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary infection was more frequent in the group of patients with NOD2/CARD15 variants. In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious effect on clinical outcome in T-cell-depleted allogeneic SCT, which is independent of GVHD. These results supports the hypothesis that the detrimental effect of NOD2/CARD15 variants in such a transplant setting might be produced by an alteration of the innate immune system more than by activation of the adaptive immune system.