Abstract
Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI).
Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed.
The transcriptome of eIV (n= 6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n= 4) and non-rejection histologic findings (n= 8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV.
Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap.
Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n= 12) and TCMRV (n= 8) samples.
The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response.
The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.