Allograft renal rejection and chemokine polymorphism

Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5,CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association,we analyzed polymorphisms of CCR5-32,CCR5-59029-A/G,CCR2-V64I and MCP-1 G/A (-2518) in 173 renal transplant recipients and 169 healthy blood donors. The patients were classified in two groups: Group-1 (G-1) included 33 HLA-identical recipients and Group-2 (G-2) included 140 (one or more) mismatched graft recipients. Forty-two patients had developed acute rejection episodes (ARs): seven in G-1 and 35 in G-2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD). The genotypic and allelic frequencies of all polymorphisms studied did not reveal significant differences between patients and controls and among G-1 and G-2 recipients. However,a significant risk of acute renal transplant rejection was found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24,95% confidence inter-val [CI],0.05-1.06; P = 0.035). There was no significant association of this polymorphism and CAD. In conclusion,the observed association of CCR2-64I with AR should be added to the spectrum of immunogenetic factors known to be involved in allograft renal loss.