Genetic variations of interleukin-23R (1143A>G) and BPI (A645G), but not of NOD2, are associated with acute graft-versus-host disease after allogeneic transplantation.
Single nucleotide polymorphisms (SNPs) in genes of the immune system predict for aGVHD and mortality after allo-SCT. We investigated the effect of SNPs in the NOD2, BPI, and IL-23R genes on posttransplantation outcome in a cohort of 304 patients. NOD2 patient and donor genotype and BPI recipient genotype were not associated with the occurrence of aGVHD. However, IL-23R-SNP in the donor was correlated with less aGVHD. This association could be confirmed in multivariate analysis (odds ratio [OR], 0.39; P = .039), which identified in vivo T cell depletion (OR, 0.32; P < .001) and multiagent GVHD prophylaxis (OR, 0.51; P = .031) as other independent factors predicting for less-severe aGVHD. This multivariate model also revealed a trend toward less aGVHD in patients receiving a BPI G allele transplant (OR, 0.60; P = .067) and in those receiving a transplant from an HLA-matched donor (OR, 0.57; P = .058). In contrast, relapse was more frequent in patients with NOD2-SNPs (46.2% for SNP vs 33.2% for wild-type; P = .020). This association was found to be of borderline significance in multivariate analysis. Neither BPI nor IL-23R genotype predicted for relapse, and none of the investigated SNPs was correlated with 5-year overall survival. In our analysis, NOD2 SNPs did not predict aGVHD, but IL-23R(1142A>G) and BPI(A645G) SNPs appeared to be promising markers in this regard. The importance of these markers in prediction models for GVHD and relapse remain to be defined in large prospective clinical trials.
Wermke
Martin
M
Department of Medicine I, University Hospital Carl-Gustav-Carus, Fetscherstraße 74, Dresden, Germany. martin.wermke@uniklinikum-dresden.de
Maiwald
Stefanie
S
Schmelz
Renate
R
Thiede
Christian
C
Schetelig
Johannes
J
Ehninger
Gerhard
G
Bornhäuser
Martin
M
Wassmuth
Ralf
R
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D014184:Transplantation, Homologous; D055815:Young Adult
C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin