title: Polymorphism of interleukin-23 receptor gene but not of NOD2/CARD15 is associated with graft-versus-host disease after hematopoietic stem cell transplantation in children.
abstract: Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The selection of a suitable donor is the most critical issue in preventing severe GVHD. Recent data suggest that the risk of GVHD does not only depend on human leukocyte antigens (HLA) but also on polymorphisms of genes that influence immune responses. We analyzed the 1142 G>A single-nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R) and 3 SNPs in the NOD2/CARD15 gene in a cohort of 231 children who underwent allogeneic stem cell transplantation and/or their respective donors. No association was observed between any of the NOD2/CARD15 polymorphisms and GVHD in either donor or recipient. Likewise, the IL23R polymorphism in the recipient was not significantly associated with GVHD. We found a significantly reduced incidence of acute GVHD (aGVHD) grade II-IV in patients who were transplanted from a donor with the IL23R polymorphism (5.0% versus 33.3%; P=.009). There was no case of aGVHD grade III-IV if this polymorphism occurred in the donor. These findings could be particularly relevant for children with inborn metabolic or immunologic disorders who do not benefit from a graft-versus-tumor effect, and therefore, selection of a donor with the IL23R polymorphism might be beneficial.
authors.affiliation: Department of Pediatrics, University of Jena, Jena, Germany. bernd.gruhn@med.uni-jena.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.forename: Juliane
authors.initials: J
authors.lastname: Intek
authors.forename: Nadine
authors.initials: N
authors.lastname: Pfaffendorf
authors.forename: Roland
authors.initials: R
authors.lastname: Zell
authors.forename: Selim
authors.initials: S
authors.lastname: Corbacioglu
authors.forename: Felix
authors.initials: F
authors.lastname: Zintl
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinbach
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin