Renal allograft immune response is influenced by patient and donor cytokine genotypes.
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.
Canossi
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CNR Institute Organ Transplant and Immunocytology, L'Aquila, Italy. a.canossi@itoi.cnr.it
Piazza
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Poggi
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Ozzella
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Di Rocco
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Papola
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Iaria
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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
D001323:Autoantibodies; D016207:Cytokines; D006680:HLA Antigens; D007371:Interferon-gamma