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


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.


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.
Granell
Miquel
M
Department of Hematology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Faculty of Medicine, University of Barcelona, Spain.
Urbano-Ispizua
Alvaro
A
Aróstegui
Juan Ignacio
JI
Fernández-Avilés
Francesc
F
Martínez
Carmen
C
Rovira
Montserrat
M
Rius
Josefa
J
Plaza
Susana
S
Gaya
Anna
A
Navarro
Alfons
A
Talarn
Carme
C
Carreras
Enric
E
Monzó
Mariano
M
Montserrat
Emili
E
Yagüe
Jordi
J
D000328:Adult; D005260:Female; D005819:Genetic Markers / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000401:mortality; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000401:mortality*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality
D005819:Genetic Markers; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein