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.
Burlingham
W J
WJ
Department of Surgery, University of Wisconsin, Madison 53792, USA.
O'Connell
P J
PJ
Jacobson
L M
LM
Becker
B N
BN
Kirk
A D
AD
Pravica
V
V
Hutchinson
I V
IV
D000293:Adolescent; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D016678:Genome; D005838:Genotype; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D004247:DNA