title: Renal allograft immune response is influenced by patient and donor cytokine genotypes.
abstract: This study investigated the impact of specific cytokine genotypes on the incidence of acute rejection episodes (ARE), chronic graft dysfunction (CGD), and anti-HLA donor-specific antibody (DS-Ab) production in 86 renal transplant recipients and 70 cadaveric donors. A PCR-SSP method was performed for the analysis of polymorphisms in TNF-alpha, IL-6, TGF-beta, IL-10, and IFN-gamma cytokines. DS-Ab monitoring of sera was performed using a FCXM analysis. Observed cytokine frequencies for patients and donors were not significantly different from the expected frequencies under Hardy-Weinberg equilibrium conditions. The evaluation in recipients revealed a higher frequency of DS-Ab-positive patients among the TNF-alpha high (50.0% vs 25.7%), and for the IL-10 cytokine a greater incidence of ARE-positive patients (35.8% vs 18.2%) with the high + intermediate, compared with the low genotype. The combined effect of these 2 genotypes predisposed to DS-Abs (71.4% vs 25.3%; P = 0.02; odds ratio [OR] = 7.37). As for the TGF-beta1 cytokine, we observed a higher number of CGD-positive patients among high compared with intermediate producers (14.3% vs 0%; P = .050). The analysis of donors revealed a significantly lower incidence of ARE-positive patients among recipients whose donors were carriers of the high IL-6 G/G-genotype compared with the G/C+C/C-genotypes (16.7% vs 41.2%; P = .03), suggesting a protective effect of the G/G genotype on ARE and a predisposing role of donor (-174)allele C. In addition, we noted an association between the IFN-gamma low A/A-genotype and a higher incidence of ARE (42.1% vs 0%; P = .002) and DS-Ab production (47.4% vs 12.5%; P = .02) compared with high producers.
authors: CNR Institute Organ Transplant and Immunocytology, L'Aquila, Italy. a.canossi@itoi.cnr.it
authors: A
authors: A
authors: Canossi
authors: A
authors: A
authors: Piazza
authors: E
authors: E
authors: Poggi
authors: G
authors: G
authors: Ozzella
authors: M
authors: M
authors: Di Rocco
authors: F
authors: F
authors: Papola
authors: G
authors: G
authors: Iaria
authors: D
authors: D
authors: Adorno
mesh_terms: D001323:Autoantibodies / Q000097:blood; D002102:Cadaver; D016207:Cytokines / Q000235:genetics*; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D006680:HLA Antigens; D007371:Interferon-gamma