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Early isolated V-lesion may not truly represent rejection of the kidney allograft
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 prog...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365629/ https://www.ncbi.nlm.nih.gov/pubmed/30287520 http://dx.doi.org/10.1042/CS20180745 |
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author | Wohlfahrtova, Mariana Hruba, Petra Klema, Jiri Novotny, Marek Krejcik, Zdenek Stranecky, Viktor Honsova, Eva Vichova, Petra Viklicky, Ondrej |
author_facet | Wohlfahrtova, Mariana Hruba, Petra Klema, Jiri Novotny, Marek Krejcik, Zdenek Stranecky, Viktor Honsova, Eva Vichova, Petra Viklicky, Ondrej |
author_sort | Wohlfahrtova, Mariana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6365629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63656292019-02-08 Early isolated V-lesion may not truly represent rejection of the kidney allograft Wohlfahrtova, Mariana Hruba, Petra Klema, Jiri Novotny, Marek Krejcik, Zdenek Stranecky, Viktor Honsova, Eva Vichova, Petra Viklicky, Ondrej Clin Sci (Lond) Research Articles 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. Portland Press Ltd. 2018-10-29 /pmc/articles/PMC6365629/ /pubmed/30287520 http://dx.doi.org/10.1042/CS20180745 Text en © 2018 The Author(s). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Research Articles Wohlfahrtova, Mariana Hruba, Petra Klema, Jiri Novotny, Marek Krejcik, Zdenek Stranecky, Viktor Honsova, Eva Vichova, Petra Viklicky, Ondrej Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title | Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title_full | Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title_fullStr | Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title_full_unstemmed | Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title_short | Early isolated V-lesion may not truly represent rejection of the kidney allograft |
title_sort | early isolated v-lesion may not truly represent rejection of the kidney allograft |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365629/ https://www.ncbi.nlm.nih.gov/pubmed/30287520 http://dx.doi.org/10.1042/CS20180745 |
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