ASSAYS TO PREDICT ALLOGRAFT REJECTION

J.C. Jeong¹, Y. Hwang², S. Hurh³, H. Kim³, H. Lee⁴, Y.J. Kim⁵, M. Kim⁵, N. Byeon⁵, M.H. Park⁶, J. Yang⁵, C. Ahn^1
1Internal Medicine, Seoul National University College of Medicine, Seoul/KOREA, ²Internal Medicine, Eulji General Hospital, Seoul/KOREA, ³Transplantation Research Institute, Seoul National University College of Medicine, Seoul/KOREA, ⁴Internal Medicine, Eulji University of Medicine, Daejon/KOREA, ⁵Transplantation Center, Seoul National University Hospital, Seoul/KOREA, ⁶Laboratory Medicine, Seoul National University College of Medicine, Seoul/KOREA

Body: Introduction: Complements play important roles in both rejection and ischemia-reperfusion injury after transplantation. C5 is one of pivotal complement proteins, which not only initiates the assembly of the membrane attack complex, C5b-9, but also mediates chemotaxis of various immune cells through interaction with its cognate receptor, C5a receptor (C5aR). We evaluated the influence of genetic variations in the C5 and its receptor C5aR of both recipients and donors on the allograft outcomes in the living donor kidney transplantation. Methods: Seven single nucleotide polymorphisms (SNPs) in C5 (rs12237774; rs2159776; rs17611; rs25681; rs2241004; rs10985126; rs10818500) and one SNP (rs10404456) in C5aR gene were genotyped in a total of 191 adult recipient-donor pairs from the SNUH kidney transplantation registry (Jan. 1996 to Aug. 2006). The association of these genetic polymorphisms with allograft outcomes (acute rejection within one year and glomerular filtration rate (GFR) estimated by simplified MDRD formula at one year after transplantation) was determined. The association of genetic polymorphisms of 4 SNPs (rs2159776; rs17611; rs25681; rs2241004) with serum C5 level was determined in 100 healthy volunteers. Results: Three SNPs (rs17611, rs25681, rs2241004) in recipient C5 gene were associated with allograft function at one year (P<0.05 after Bonferroni correction). C5 gene consisted of four linkage disequilibrium (LD) blocks. There were four haplotypes (haplotype, frequency: AATA, 0.516; GGCG, 0.269; GGCA, 0.180; AGCA, 0.023) in the second LD block which was formed by four SNPs (rs2159776; rs17611; rs25681; rs2241004). Two haplotypes (GGCG/AGCA) in recipient C5 were significantly associated with reduced GFR at one year (51.6 ± 12.5, 62.6 ± 15.6, and 67.1 ± 15.3 ml/m/1.73m² in the recipients with two, one and no risk haplotypes, respectively; P<0.001). However, the genetic polymorphisms in neither C5 nor C5aR genes were associated with the risk for the occurrence of acute rejection within one year. Donor polymorphisms had no influence on the allograft outcomes. Neither 4 SNPs (rs2159776; rs17611; rs25681; rs2241004) nor haplotypes(GGCG/AGCA) were significantly correlated with serum C5 level in healthy volunteers. Conclusion: The GGCG/AGCA haplotypes of complement 5 in recipients were associated with lower renal allograft function.

Disclosure: All authors have declared no conflicts of interest.