An Experimental Study Of The Relationship Between Cytokine Genotype And Chronic Allograft Nephropathy

The concrete role of cytokine gene polymorphisms in predicting the effect of renal transplantation has not yet been completely clarified.It has been reported that tumor necrosis factor-alpha(TNF-α) is associated with acute rejection following renal transplatation, while transforming growth factor-beta(TGF-β1) is associated with acute rejection and chronic allograft nephropathy following renal transplatation.And Interferon-gamma is associated with chronic allograft nephropathy following renal transplatation.In order to access the relationship between these two cytokines levels and their genotypes,and to investigate the role of cytokine gene polymorphisms in predicting the effect of kidney transplantation, plasma cytokines levels were observed by the means of enzyme-linked immunosorbent assay with avidin-biotin-HRP (horse radish peroxidase) complex (ELISA) and polymerase chain reaction with sequence specific premier(PCR-SSP).As a result,the plasma levels of cytokines rose increasingly with the change of cytokines producer genotype from low to high. The plasma level of IFN-γin high producer genotype (57.18±9.16pg/ml) was significantly higher than that in low producer genotype (31.86±5.67pg/ml,P<0.01).The plasma level of TGF-β1 progressively increase with the change of TGF-β1 producer genotype from low, moderate to high(131.3±63.8,462.3±72.4,998.7±83.4ng/ml, respectively;P<0.01).Similarly.a greater proportion of the receptors with IFN-γhigh producer genotype had CAN (42.2%,35/83) compared with receptors with the IFN-γlow producer genotype(12.8%,χ2=10.370, P<0.05).Similarly, a greater proportion of receptors with TGF-β1 high producer genotype had CAN compared with receptors with the TGF-β1 low producer genotype(P<0.01). and receptors'TNF-α,IL-6,IL-10 genotypes were not associated with chronic allograft nephropathy.Similarly,the chronic allograft nephropathy incidence of donors with high TGF-β1 producer genotype was 44.4%,the rate in those with low TGF-β1 producer genotype was 28.7%. There were not difference between these two groups.Also there was not difference between donors with high IFN-γproducer genotype and with low IFN-γproducer genotype after statistics calculation.A greater proportion of the recipients with themselves'IFN-γhigh/their corresponding donors'IFN-γhigh producer genotype(3/4,75%)had chronic allograft nephropathy as compared with all other genotypes(29/106,27.4%;χ2=7.935,P<0.01) Conversely, significantly fewer patients with themselves'IFN-γlow/ their corresponding donors'IFN-γlow producer genotype(11/59,18.6%)had chronic allograft nephropathy as compared with all other genotypes(24/55,43.6%;P<0.01). A greater proportion of the recipients with themselves'TGF-β1 high/their corresponding donors'TGF-β1 high producer genotyp(e4/4,100%)had chronic allograft nephropathy as compared with all other genotypes(31/110,28.2%;χ2=9.357,P<0.01) Conversely, significantly fewer patients with themselves'TGF-β1 low/ their corresponding donors'TGF-β1 low producer genotype(12/61,19.7%)had chronic allograft nephropathy as compared with all other genotypes(23/53,43.4%;P<0.01).In the relationship with using immune suppression, a greater proportion of the recipients with IFN-γhigh producer genotype/CsA low dosage(23/31,74.2%)had chronic allograft nephropathy compared with recipients with the other IFN-γgenotype/CsA dosage(19/91,20.9%;P<0.01).However,no associations were found with the presence of chronic allograft nephropathy and the IFN-γgenotype/CsA dosage between IFN-γlow producer genotype/CsA high dosage(36.4%,4/11)and IFN-γlow producer genotype/CsA mediate dosage(17.3%,13/75;P>0.05).Similarly, significantly associations were found with the presence of chronic allograft nephropathy and the TGF-β1 high producer genotype/CsA low dosage(15/25,60%)and other combination with TGF-β1 producer genotype and CsA dosage(27.8%,27/97;P>0.05).No associations were found with the presence of chronic allograft nephropathy and the TGF-β1 high producer genotype/CsA high dosage(1/3,33.3%)and other combination with TGF-β1 producer genotype and CsA dosage(34.5%,41/119;P>0.05).Just as the same, no associations were found with the presence of chronic allograft nephropathy and the TGF-β1 low producer genotype/CsA high dosage(7/16,43.8%)and other combination with TGF-β1 producer genotype and CsA dosage(24.4%,19/78;P>0.05)These data suggest that:1) IFN-γ,TGF-β1 genotypes are determinants of their corresponding serum levels in healthy adult people.2) The recipient IFN-γand TGF-β1 genotypes are determinants of chronic allograft nephropathy following kidney transplantation.3) The donor genotype is not associate with chronic allograft nephropathy following kidney transplantation.4) If the recipients with IFN-γhigh or TGF-β1 high producer genotype were treated with CsA high dosage following allograft,the rate of chronic allograft nephropathy would be less. Conversely, the recipients with IFN-γlow or TGF-β1 low producer genotype had no necessary to use CsA high dosage.Therefore, routine screening of these cytokines genotype may have an important clinical significance in identifying patients at risk of chronic allograft nephropathy, providing an efficient measure to allocate kidney more rationally and guiding the more reasonable individual use of immunosuppression following kidney transplantation.