The role of CYP3A5 and MDR1-C3435T polymorphisms on calcineurine inhibitors : Evidence of a direct effect on the clinical outcome during the first year after kidney transplant

Having defined CTL-associated transcripts (CATs) in CTL in vitro, we used microarrays to quantify the burden of CAT sets compared with individual transcripts in human renal transplant biopsies with T-cell mediated rejection (TCMR). CAT sets in TCMR resembled diluted CTL RNA, maintaining overall hierarchy of expression relative to CTL in vitro. NK selective sets were not detected in TCMR, indicating the CATs mainly reflect T cells. We selected 25 highly expressed CATs that diluted quantitatively in kidney RNA (QCATs) and remained detectable after 32-fold dilution. QCAT burden in 14 kidneys with TCMR was 3 to 15% of CTL RNA, correlating with infiltration. One biopsy diagnosed as TCMR only by endothelialitis had little interstitial infiltrate and lowest CAT burden. CAT sets were more consistent than individual CATs such as perforin or granzyme B, which showed heterogeneity. In luster and principal component analysis, QCATs grouped biopsies with TCMR together, in close relationship to in vitro CTL. Thus QCAT sets robustly measure the burden of CTL and effector memory T cells in biopsies as %CTL RNA, in a manner not achieved by measurement of individual transcripts.