Tumor necrosis factor-alpha and tumor growth factor-beta1 genotype: partial association with intragraft gene expression in two cases of long-term peripheral tolerance to a kidney transplant.

Genomic DNA was obtained from peripheral blood samples of patients JB and DS each of whom received a kidney transplant at 16 years of age from a serologically HLA-DR matched and HLA-class I -mismatched donor. Both patients discontinued immunosuppression after 1-2 years and retained good renal function for an additional 5 years or more. DNA was analyzed for genetic polymorphisms in the tumor necrosis factor-alpha (TNFalpha) and tumor growth factor-beta1 (TGFbeta1) loci. Biopsy samples obtained during stable function (DS, JB) and during rejection (JB) were analyzed by RT/PCR for cytokine gene expression. Both patients had a high responder genotype for TGFbeta1. DS had a low responder TNFalpha genotype, while JB and his donor were both genotypically TNFalpha intermediate responders. DS had a high TGFbeta1: TNFalpha mRNA ratio in two biopsies obtained during tolerance, while JB, who eventually lost his graft, had more TNFalpha than TGFbeta1 mRNA. The results suggest a possible role for cytokine immunogenetics in the stability of peripheral tolerance.