Wohlfahrtova, Mariana and Hruba, Petra and Klema, Jiri and Novotny, Marek and Krejcik, Zdenek and Stranecky, Viktor and Honsova, Eva and Vichova, Petra and Viklicky, Ondrej

Wohlfahrtova, M., Hruba, P., Klema, J., Novotny, M., Krejcik, Z., Stranecky, V., … Viklicky, O. (2018). Early isolated V-lesion may not truly represent rejection of the kidney allograft. Clinical Science, 132(20), 2269–2284.

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.

Citation

@article{wohlfahrtova2018,
  author = {Wohlfahrtova, Mariana and Hruba, Petra and Klema, Jiri and Novotny, Marek and Krejcik, Zdenek and Stranecky, Viktor and Honsova, Eva and Vichova, Petra and Viklicky, Ondrej},
  title = {{Early isolated V-lesion may not truly represent rejection of the kidney allograft}},
  journal = {Clinical Science},
  volume = {132},
  number = {20},
  pages = {2269-2284},
  year = {2018},
  month = oct,
  issn = {0143-5221},
  doi = {10.1042/CS20180745},
  url = {https://doi.org/10.1042/CS20180745},
  eprint = {https://portlandpress.com/clinsci/article-pdf/132/20/2269/450443/cs-2018-0745.pdf}
}