title: Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant.
abstract: The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ² = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.
authors.affiliation: Immunogenetic applied to cells therapy Research Unit, Immunohaematology and HLA-Typing Department, National Blood Transfusion Centre of Tunis, Tunis, Tunisia. sellamimh@laposte.net
authors.forename: Mohamed Hichem
authors.initials: MH
authors.lastname: Sellami
authors.forename: Meriem
authors.initials: M
authors.lastname: Bani
authors.forename: Lamia
authors.initials: L
authors.lastname: Torjemane
authors.forename: Houda
authors.initials: H
authors.lastname: Kaabi
authors.forename: Saloua
authors.initials: S
authors.lastname: Ladeb
authors.forename: Tarek
authors.initials: T
authors.lastname: Ben Othmane
authors.forename: Slama
authors.initials: S
authors.lastname: Hmida
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D035781:Siblings; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014416:Tunisia; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; D015778:Minor Histocompatibility Antigens