Abstract
Episodes of acute rejection (aRx) may occur in functional renal allografts even at a very late stage post-Tx. Histopathology in early and late aRx looks quite similar--however, there is a slower deterioration of graft function in late aRx, suggesting that pathogenetic immune mechanisms are different. In order to investigate this phenomenon we studied the gene expression pattern (IL-1beta, 2, 4, 8, 10, IFNgamma, TNFalpha, GrnA, IL-2R p55/p75) in PBMC and core biopsies from long-term renal allograft recipients with histologically proven late aRx and compared it with transplant and non-transplant controls using a semiquantitative RT-PCR technique. PBMC and graft-infiltrating cells of patients with late aRx showed an upregulation, especially of IFN-gamma, IL-4, IL-10, and TNFalpha transcripts. While IL-2 mRNA was only detected in PBMC of two patients with late aRx who were not on cyclosporine, upregulation of intragraft IL-2 mRNA allowed the best discrimination between aRx and the other groups (sensitivity: 83%, specificity: 93%). In contrast to several reports on early Rx we did not notice an elevation of granzyme A transcripts in comparison with the controls, suggesting that cell-mediated inflammatory processes (CD4+ T cell-media...Continue Reading
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