title: (AT) repeat in the 3' untranslated region of the CTLA-4 gene and susceptibility to acute allograft rejection in Tunisian renal transplantation.
abstract: Allograft rejection is an immune response relying on the proliferation and the differentiation of T cells. CTLA-4 is a co-stimulatory molecule, expressed on activated T lymphocytes, which has been shown to play a crucial role in the down-regulation of T-cell activation. Herein, we have examined the impart of a genetic marker in the CTLA-4 gene on renal transplant outcomes. A cohort of 144 renal recipients and 100 healthy subjects were genotyped by the fragments analysis method using an automated sequencer. Patients were classified into two groups: Group I included 31 HLA-identical haplotype allograft recipients and Group II, 113 showing one or more HLA haplotype mismatches. Forty patients (27.78%) developed at least one acute rejection episode (ARE): 9 in Group I and 31 in Group II. Before transplantation, 20 patients were lymphocytotoxic antibodies (LCT) positive: 4 Group I, 2 of whom developed an ARE, and sixty in Group II, including 8 with an ARE. The occurrence of an ARE was associated with the presence of LCT before transplantation among the entire cohort of patients (P = .032) and among Group II (P = .037). The allelic frequencies of (AT)n polymorphism did not reveal significant differences between patients and controls. The most prevalent alleles were the 88 bp (51% in controls and 44.44% in patients) and the 106 bp (8% and 10.76%, respectively). We noticed an increase of the 120 bp allele frequency among patients who had undergone an ARE compared with those who did not display this complication (8.75% vs 3.85%). Likewise, among LCT-negative Group I, recipients the incidence of the 120 bp allele was higher in ARE than non-ARE patients. Although the differences were not statistically significant, we propose that the 120 bp allele of the CTLA-4 gene (AT)n microsatellite a predisposes to acute rejection episodes in renal transplantation.
authors.affiliation: Immunology Research, Laboratory of Kidney Transplantation and Immunopathology (Laboratoire de Recherche: LR03SP01), Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Krichen
authors.forename: I
authors.initials: I
authors.lastname: Sfar
authors.forename: H
authors.initials: H
authors.lastname: Hadj Kacem
authors.forename: R
authors.initials: R
authors.lastname: Bardi
authors.forename: S
authors.initials: S
authors.lastname: Jendoubi-Ayed
authors.forename: M
authors.initials: M
authors.lastname: Makhlouf
authors.forename: T
authors.initials: T
authors.lastname: Ben Romdhane
authors.forename: F
authors.initials: F
authors.lastname: Besseghair
authors.forename: H
authors.initials: H
authors.lastname: Aouadi
authors.forename: T
authors.initials: T
authors.lastname: Ben Abdallah
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
authors.forename: K
authors.initials: K
authors.lastname: Ayed
authors.forename: Y
authors.initials: Y
authors.lastname: Gorgi
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014184:Transplantation, Homologous; D014416:Tunisia
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human