Tumor necrosis factor-α and tumor growth factor-β1 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 (TNF-alpha) and tumor growth factor-beta 1 (TGF beta 1) 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 TGF beta 1. DS had a low, responder TNF alpha genotype, while JB and his donor were both genotypically TNF alpha intermediate responders. DS had a high TGF beta 1: TNF alpha mRNA ratio in two biopsies obtained during tolerance, while JB, who eventually lost his graft, had more TNF alpha than TGF beta 1 mRNA. The results suggest a possible role for cytokine immunogenetics in the stability of peripheral tolerance.