The overall objective of this project is to characterize the molecular effector mechanisms of human renal allograft rejection, the most frequent serious complication of renal transplantation. The hypothesis that the rejection of renal allografts can be anticipated, confirmed, and reversibility or recurrence prognosticated by quantitative mRNA phenotyping and by measurement of cytokines will be explored in this study.
The specific aims are:
Specific Aim 1 : To test the hypothesis that acute rejection of human renal allografts can be anticipated by sequential evaluation of renal allograft recipients for the expression of granzyme B, a killer cell specific serine protease, interleukin-2 (IL-2) and transforming growth factorbeta (TGFbeta).
Specific Aim 2 : To examine the proposition that quantification of selected gene expression will reflect human renal allograft status as determined by percutaneous core needle biopsy of the graft, as well as predict the response to anti-rejection therapy (high dose corticosteroid or anti-CD3 mAb) provided to the graft recipients.
Specific Aim 3 : To test the supposition that an evaluation for the T-cell receptor beta chain variable region gene (TCR Vbeta) usage might predict the response to anti-CD3 mAb therapy provided to patients with either corticosteroid resistant rejection or recurrent (rebound) rejection. This will be tested by PCR quantification of TCR Vbeta usage by graft infiltrating T-cells, obtained prior to and after completion of anti- rejection therapy.
