Cytokines are immunomodulatory proteins, or glycoproteins, that are able to control and modulate the activities of cells of the immune system in a complex network of interactions. In renal transplantation, although rejection is mediated by recipient lymphocytes or by donor-specific anti-HLA antibody production, the local environment in which an antigen-lymphocyte interaction takes place is influenced by both donor and recipient factors and cytokines are the major determinant of this milieu. There is now evidence that the production of many cytokines is under genetic control and that polymorphisms exist in a large number of these genes (coding regions, introns or promoter regions). The purpose of this study was to clarify the effects of both recipient and donor genotypes on the outcome of renal transplantation. In particular, by genotyping methods with sequence-specific primers (PCR-SSP) 58 cadaveric renal transplant donor-recipient pairs were investigated in order to evaluate the impact of donor and recipient gene polymorphisms of TNF-a (-308, G/A), IL-6 (-174, C/G), TGF-b (codons 10, 25 in exon 1), IL-10 (-1082, -819, -592 in promoter) and IFN-g (+874 in intron 1) on the incidence and severity of acute rejection (AR) and the production of donor-specific antibody (DS-Ab) within the first year after renal transplantation. The presence of class I and II DS-Abs was carried out using flow cytometry crossmatch monitoring (FCXM).
The Institute carries out most of its activity in Transplant Immunology and Histocompatibility field. This study was performed by collaboration with Rome Section of Institute and Clinical Surgery of Tor Vergata University of Rome.
Analysis in the recipients showed that IL-10high+int together with TNF-a high, IL-10 high with TNF-a high genotypes predisposed them to antibody production (p=0.0036 and p=0.04, respectively) while the combination of IL-10 high+int and IFN-g high+int was associated with acute rejection (43% vs 17% p=0.013). On the contrary, in donors we noticed an unexpected result for the IFN-g low genotype that predisposed either to rejection and antibody production: in fact, the percentage of low producers was 19.4% in controls and 23.3% in ARneg, which increased significantly to 46.7% in the ARpos group (p = 0.0058 and p = 0.0087, respectively), while the frequency of the low producers was 40% in Abpos compared to 19.4% in the control group (p = 0.033). In addition, IL-10 high+int and IFN-g high+int protected from acute rejection (p=0.033), while the combination of IL-10 high and IFN-g low predisposed individuals to antibody production (p=0.014). These data evidence that the combined analysis of donor/recipient cytokine genotypes enable a better evaluation of results.
Focus