Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts

Abstract The Banff 2019 kidney allograft pathology update excluded isolated tubulitis without interstitial inflammation (ISO-T) from the category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. In this study, we explored the molecular asses...

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Autores principales:	Petra Hruba, Katellyn Madill-Thomsen, Martina Mackova, Jiri Klema, Jana Maluskova, Ludek Voska, Alena Parikova, Janka Slatinska, Philip F. Halloran, Ondrej Viklicky
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Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa45873e82da4b13837a9070dabff930
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spelling	oai:doaj.org-article:aa45873e82da4b13837a9070dabff9302021-12-02T11:57:58ZMolecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts10.1038/s41598-020-79332-92045-2322https://doaj.org/article/aa45873e82da4b13837a9070dabff9302020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79332-9https://doaj.org/toc/2045-2322Abstract The Banff 2019 kidney allograft pathology update excluded isolated tubulitis without interstitial inflammation (ISO-T) from the category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. In this study, we explored the molecular assessment of ISO-T. ISO-T or interstitial inflammation with tubulitis (I + T) was diagnosed in indication biopsies within the first 14 postoperative days. The molecular phenotype of ISO-T was compared to I + T either by using RNA sequencing (n = 16) or by Molecular Microscope Diagnostic System (MMDx, n = 51). RNA sequencing showed lower expression of genes related to interferon-y (p = 1.5 10–16), cytokine signaling (p = 2.1 10–20) and inflammatory response (p = 1.0*10–13) in the ISO-T group than in I + T group. Transcripts with increased expression in the I + T group overlapped significantly with previously described pathogenesis-based transcript sets associated with cytotoxic and effector T cell transcripts, and with T cell-mediated rejection (TCMR). MMDx classified 25/32 (78%) ISO-T biopsies and 12/19 (63%) I + T biopsies as no-rejection. ISO-T had significantly lower MMDx scores for interstitial inflammation (p = 0.014), tubulitis (p = 0.035) and TCMR (p = 0.016) compared to I + T. Fewer molecular signals of inflammation in isolated tubulitis suggest that this is also a benign phenotype on a molecular level.Petra HrubaKatellyn Madill-ThomsenMartina MackovaJiri KlemaJana MaluskovaLudek VoskaAlena ParikovaJanka SlatinskaPhilip F. HalloranOndrej ViklickyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Petra Hruba Katellyn Madill-Thomsen Martina Mackova Jiri Klema Jana Maluskova Ludek Voska Alena Parikova Janka Slatinska Philip F. Halloran Ondrej Viklicky Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
description	Abstract The Banff 2019 kidney allograft pathology update excluded isolated tubulitis without interstitial inflammation (ISO-T) from the category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. In this study, we explored the molecular assessment of ISO-T. ISO-T or interstitial inflammation with tubulitis (I + T) was diagnosed in indication biopsies within the first 14 postoperative days. The molecular phenotype of ISO-T was compared to I + T either by using RNA sequencing (n = 16) or by Molecular Microscope Diagnostic System (MMDx, n = 51). RNA sequencing showed lower expression of genes related to interferon-y (p = 1.5 10–16), cytokine signaling (p = 2.1 10–20) and inflammatory response (p = 1.0*10–13) in the ISO-T group than in I + T group. Transcripts with increased expression in the I + T group overlapped significantly with previously described pathogenesis-based transcript sets associated with cytotoxic and effector T cell transcripts, and with T cell-mediated rejection (TCMR). MMDx classified 25/32 (78%) ISO-T biopsies and 12/19 (63%) I + T biopsies as no-rejection. ISO-T had significantly lower MMDx scores for interstitial inflammation (p = 0.014), tubulitis (p = 0.035) and TCMR (p = 0.016) compared to I + T. Fewer molecular signals of inflammation in isolated tubulitis suggest that this is also a benign phenotype on a molecular level.
format	article
author	Petra Hruba Katellyn Madill-Thomsen Martina Mackova Jiri Klema Jana Maluskova Ludek Voska Alena Parikova Janka Slatinska Philip F. Halloran Ondrej Viklicky
author_facet	Petra Hruba Katellyn Madill-Thomsen Martina Mackova Jiri Klema Jana Maluskova Ludek Voska Alena Parikova Janka Slatinska Philip F. Halloran Ondrej Viklicky
author_sort	Petra Hruba
title	Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
title_short	Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
title_full	Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
title_fullStr	Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
title_full_unstemmed	Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
title_sort	molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/aa45873e82da4b13837a9070dabff930
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Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts

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