Chemokine and receptor-gene expression during early and late acute rejection episodes in human cardiac allografts

Abstract

Background: The expression levels of several chemokine genes in heart allografts correlate with histologic rejection grade. Potential molecular differences between early and late rejection (grade > or =2) episodes were examined by testing chemokine and receptor-gene expression.

Methods: Expression of inducible protein (IP)-10, monokine induced by IFN-gamma (Mig), interferon inducible-T cell alpha chemoattractant (I-TAC), regulated on activation normal T-cell expressed and secreted(RANTES), and their receptors CXCR3 and CCR5 was tested in 60 endomyocardial biopsies from 24 patients using quantitative (Taqman) real-time polymerase chain reaction (PCR). The biopsies were taken in the first 3 months or from the 9th to the 12th month following transplantation.

Results: IP-10, Mig, RANTES, CXCR3, and CCR5 expression levels were increased in the later versus earlier biopsies (P< or =0.01) despite no change in histologic rejection-grade status. CONCLUSION These results demonstrate significantly increased expression of T-cell chemoattractants in heart allografts during later rejection when compared with episodes occurring shortly after transplantation. The findings suggest increased intensity of inflammation in rejection occurring at later times posttransplant that are revealed by molecular analyses of the graft.