The aim of this pilot study was to investigate whether acute rejection after liver transplantation is associated with known single-nucleotide polymorphisms (SNPs) in the CD86- and CTLA-4 genes of liver-transplant donors and recipients. Single nucleotide polymorphisms were determined in 135 liver transplant recipients and in 73 donors. Acute rejection was not associated with CD86+ 1057 G/A genotype distributions in donors and in recipients. In univariate analysis recipient CTLA-4 -318 G/T and +49 A/G genotype distributions were both weakly associated with acute rejection. Multivariate analysis revealed that the CTLA-4 +49 SNP, but not the -318 SNP, was independently of other risk factors associated with acute rejection. Only one out of 13 CTLA-4 +49 G-homozygotes (8%) experienced acute rejection(s) compared with 40% of A/A or A/G recipients. The CTLA-4 +49 A/G SNP, which results in an amino acid substitution in the signal peptide of the protein, did not, however, affect intracellular expression or trafficking of CTLA-4 in T cells, nor soluble serum CTLA-4 concentrations of the liver transplant recipients. In conclusion, this pilot study suggests that liver transplant recipients homozygous for CTLA-4 +49 G have a reduced risk of acute rejection.

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American Journal of Transplantation
Department of Surgery

de Reuver, P., Pravica, V., Hop, W., Boor, P., Metselaar, H., Hutchinson, I., … Kwekkeboom, J. (2003). Recipient CTLA-4 +49 G/G Genotype Is Associated with Reduced Incidence of Acute Rejection after Liver Transplantation. American Journal of Transplantation, 3(12), 1587–1594. doi:10.1046/j.1600-6135.2003.00261.x