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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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79332-9 |
| _version_ | 1818752370324013056 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:50:23Z |
| format | Article |
| id | doaj.art-aa45873e82da4b13837a9070dabff930 |
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| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:50:23Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-aa45873e82da4b13837a9070dabff9302022-12-21T21:20:26ZengNature PortfolioScientific Reports2045-23222020-12-011011810.1038/s41598-020-79332-9Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allograftsPetra Hruba0Katellyn Madill-Thomsen1Martina Mackova2Jiri Klema3Jana Maluskova4Ludek Voska5Alena Parikova6Janka Slatinska7Philip F. Halloran8Ondrej Viklicky9Transplant Laboratory, Institute for Clinical and Experimental MedicineAlberta Transplant Applied Genomics CentreAlberta Transplant Applied Genomics CentreDepartment of Computer Science, Faculty of Electrical Engineering, Czech Technical UniversityDepartment of Pathology, Institute for Clinical and Experimental MedicineDepartment of Pathology, Institute for Clinical and Experimental MedicineDepartment of Nephrology, Transplant Centre, Institute for Clinical and Experimental MedicineDepartment of Nephrology, Transplant Centre, Institute for Clinical and Experimental MedicineAlberta Transplant Applied Genomics CentreTransplant Laboratory, Institute for Clinical and Experimental MedicineAbstract 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.https://doi.org/10.1038/s41598-020-79332-9 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-79332-9 |
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