CTLA-4 Exon one +49 A/G gene variants in patients with superficial and invasive bladder cancer: a study in southern Iran

Cytotoxic T-cell lymphocyte antigen 4 [CTLA-4] is a member of the superfamily of immunoglobulins that are mainly expressed by activated T cells. It is established that blockade of CTLA-4 receptors leads to the enhancement of an immune response. Different polymorphisms of the CTLA-4 gene have been described which cause increased susceptibility to various malignancies such as lymphoma or multiple myeloma. Considering that bladder cancer is one of the most prevalent cancers worldwide, we have evaluated the role of CTLA-4 gene polymorphism at position +49 A/G in the formation or progression of bladder cancer in southern Iran. A total of 226 individuals between February 2005 and June 2006 were included and placed into two subgroups: patients diagnosed with bladder cancer and a control group. Demographic data and risk factors were collected from both groups. The DNA of all subjects was extracted from their blood samples. Different genotypes of the CTLA-4 gene were determined using the restriction fragment length polymorphism [RFLP] technique and data were compared in both groups by using Pearson's chi-square test. The prevalence of AA, AG and GG genotypes at position 49, according to the PCR-RFLP method, were 57.5%, 37.2% and 5.3% in the control group, respectively. In the patient group, the prevalence of these genotypes was: AA in 57.5%, AG in 32.7% and GG in 9.8%. Statistical analysis of data showed no significant difference in both groups [P value=0.40]. Also there was no correlation between different genotypes of the CTLA-4 gene and invasiveness of the disease in our cases. Although polymorphism of the CTLA-4 gene at position 49 of exon-1 increases susceptibility to several malignancies, our study showed no relationship between polymorphism at this position and genetic susceptibility to the development of bladder cancer, nor was there any association with disease progression

Can thymic tissue induce tolerance to kidney allografts?

The aim of this study was to investigate the beneficial effect of donor thymic tissue to induce tolerance in thymokidney allografts, transplanted to thymectomized cross-bred canines. Seven pairs of transplant donors and recipients were selected from 3- to 4-month-old cross-bred canines with major histocompatibility complex [MHC] mismatches. Recipients underwent partial thymectomy 4 weeks before transplantation and received an autologous thymic graft under the renal capsule, which had been engrafted in the donors 3 months before transplantation [thymokidney]. Successful engraftment with evidence of thymocyte development in the donors was determined by gross and histologic examination at the time of transplantation. Biopsy specimens were obtained at the transplant day and 3 months after transplantation and were studied histologically for evidence of hyperacute or acute rejection. At 90 days after the operation, all 7 juvenile thymic grafts had developed with normal thymic structure under the renal capsule. Hyperacute rejection was not observed in allografts, and all of them were functioning until the end of follow-up; however, all of the allografts showed acute cell-mediated rejection 3 months after transplantation. No tolerance was induced by vascularized donor thymokidneys in MHCmismatched canines. The advantages of tolerance over chronic immunosuppression are so great that a potentially tolerogenic approach such as thymic transplantation would seem worthy of further investigations on large animal models. To evaluate the beneficial effects of thymic tissue in tolerance induction, utilizing a short course, lowdose adjuvant immunosuppressant to this regimen and/or application of in-bred MHCmatched canines is suggested