title: Polymorphisms in CCR6 are associated with chronic graft-versus-host disease and invasive fungal disease in matched-related hematopoietic stem cell transplantation.
abstract: Graft-versus-host disease (GVHD) and fungal infections are frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT). Single nucleotide polymorphisms (SNPs) in genes of the immune system can influence the inflammatory cascade and T cell-driven alloimmune reactions after HSCT, and thus increasing the incidence of GVHD and infectious complications. Here, we investigated the effect of SNPs in IL-23R and CCR6 on posttransplantation outcome in 161 recipients of partially T cell-depleted HSCT. Remarkably, IL-23R SNPs were not associated with clinical outcome, but we found that disparities in the CCR6 tagSNP rs2301436 and SNP rs3093023 are independently associated with the occurrence of chronic GVHD (cGVHD) and invasive fungal disease. In multivariate analysis, patients receiving a transplant from a homozygous rs2301436 G allele donor showed less cGVHD (odds ratio [OR]: 0.16; P = .002), as was the case for a homozygous donor rs3093023 G allele (OR: 0.24; P = .005). In parallel, the GG genotype at rs2301436 in donors was associated with a higher incidence of invasive fungal disease at day 100 after HSCT (OR: 3.59; P = .008). This study shows that CCR6 SNPs can be used to predict clinical outcome, and that polymorphisms in the CCR6 gene may influence T cell-mediated immune reactions after HSCT.
authors.affiliation: Department of Laboratory Medicine, Hematology Laboratory, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Kelly
authors.initials: K
authors.lastname: Broen
authors.forename: Anniek B
authors.initials: AB
authors.lastname: van der Waart
authors.forename: Annelies
authors.initials: A
authors.lastname: Greupink-Draaisma
authors.forename: Julia
authors.initials: J
authors.lastname: Metzig
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.forename: Nicolaas P M
authors.initials: NP
authors.lastname: Schaap
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Blijlevens
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: Harry
authors.initials: H
authors.lastname: Dolstra
mesh_terms: D000328:Adult; D000483:Alleles; D002908:Chronic Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000235:genetics* / Q000276:immunology; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D054399:Receptors, CCR6 / Q000235:genetics* / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: C106311:CCR6 protein, human; C515500:IL23R protein, human; D054399:Receptors, CCR6; D018123:Receptors, Interleukin