title: The COX-2 gene promoter polymorphism -765 delays CD4 T-cell reconstitution after lymphocyte depletion with antithymocyte globulins.
abstract: Polyclonal antithymocyte globulins (ATG) induce persistent changes in T-lymphocyte subsets characterized by low CD4 T. The mechanisms remain partly unknown. Prostaglandin E(2) (PGE(2)) is involved in lymphocyte homeostasis. Whether PGE(2) may be involved in persistent CD4 T-cell lymphopenia after ATG is unknown. We examined the association between this polymorphism and CD4 T-cell count in 159 renal transplant recipients (RTR) who received ATG. Analysis of these patients identified 6 CC (3.8%), 32 GC (22.6%), and 117 GG (73.6%) genotypes. Patients with the GG genotype had significantly higher serum PGE(2) concentrations, leading us to compare C carriers with GG patients. Carriers of the C allele had lower CD4 T cell count 1 year (235 ± 96 vs 323 ± 227/mm(3); p = 0.022) and 2 years posttransplant (325 ± 79 vs 422 ± 231/mm(3); p = 0.024). In multivariate analysis, the C allele (p = 0.029) conferred an increased risk of posttransplant CD4 T-cell lymphocytopenia. Pretransplant T-cell receptor excision circle levels were lower in C carriers. COX-2 gene promoter polymorphism at position -765 (G → C) is associated with persistent CD4 T-cell lymphopenia after ATG in RTR. This effect is likely to be mediated by the actions of PGE(2) on thymus function and viability.
authors.affiliation: INSERM, UMR645, Besançon, F-25020 France. dducloux@chu-besancon.fr
authors.forename: Cécile
authors.initials: C
authors.lastname: Courivaud
authors.forename: Jamal
authors.initials: J
authors.lastname: Bamoulid
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiberghien
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chalopin
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.forename: Didier
authors.initials: D
authors.lastname: Ducloux
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D000961:Antilymphocyte Serum; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human