Tumor necrosis factor-alpha and tumor growth factor-beta 1 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 D S each of whom received a kidney transplant at 16 years of age from a serol ogically HLA-DR matched and HLA-class I -mismatched donor, Both patients di scontinued immunosuppression after 1-2 years and retained good renal functi on for an additional 5 years or more. DNA was analyzed for genetic polymorp hisms in the tumor necrosis factor-alpha (TNF-alpha) and tumor growth facto r-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 ge ne 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 bot h 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. Th e results suggest a possible role for cytokine immunogenetics in the stabil ity of peripheral tolerance.