title: Impact of inflammatory cytokine gene polymorphisms on developing acute graft-versus-host disease in children undergoing allogeneic hematopoietic stem cell transplantation.
abstract: Single nucleotide polymorphisms (SNPs) in gene encoding pro- and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II-IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the use of peripheral CD34+ cells as stem cell source. The multivariate analysis confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD grades II-IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III-IV. In conclusion we found an association between IL10, FAS, and TLR4 in the donor and IL18 in the recipient and an increased risk of developing aGvHD in transplanted children. Knowledge of the SNPs of cytokine genes associated with aGvHD represents a useful tool for an integrated pretransplantation risk assessment and could guide the physicians to an optimal and more accurate HSCT planning.
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Daniele
authors.identifier: 0000-0002-9895-5942
authors.initials: D
authors.lastname: Zama
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy ; "G. Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Milena
authors.identifier: 0000-0002-3364-9098
authors.initials: M
authors.lastname: Urbini
authors.affiliation: "G. Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Libri
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vendemini
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: William
authors.identifier: 0000-0002-4833-4128
authors.initials: W
authors.lastname: Morello
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rondelli
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Prete
authors.affiliation: Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna Sant'Orsola-Malpighi Hospital, No. 11, 40138 Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014184:Transplantation, Homologous; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; C508609:IL10 protein, human; D020382:Interleukin-18; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019014:fas Receptor; D016753:Interleukin-10