The COX-2 gene promoter polymorphism -765 delays CD4 T-cell reconstitution after lymphocyte depletion with antithymocyte globulins

Polyclonal antithymocyte globulins (ATG) induce persistent changes in T-lymphocyte subsets characterized by low CD4 T. The mechanisms remain partly unknown. Prostaglandin E2 (PGE2) is involved in lymphocyte homeostasis. Whether PGE2 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 PGE2 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/mm3; p = 0.022) and 2 years posttransplant (325 ± 79 vs 422 ± 231/mm3; 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 PGE2 on thymus function and viability.