Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants

Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patient...

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Autores principales:	Eva Vonbrunn, Tajana Ries, Stefan Söllner, Janina Müller-Deile, Maike Büttner-Herold, Kerstin Amann, Christoph Daniel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42e35ca04e0d403eb6a67e41362a8977
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spelling	oai:doaj.org-article:42e35ca04e0d403eb6a67e41362a89772021-12-02T16:06:42ZMultiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants10.1038/s41598-021-94954-32045-2322https://doaj.org/article/42e35ca04e0d403eb6a67e41362a89772021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94954-3https://doaj.org/toc/2045-2322Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.Eva VonbrunnTajana RiesStefan SöllnerJanina Müller-DeileMaike Büttner-HeroldKerstin AmannChristoph DanielNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Vonbrunn Tajana Ries Stefan Söllner Janina Müller-Deile Maike Büttner-Herold Kerstin Amann Christoph Daniel Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
description	Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.
format	article
author	Eva Vonbrunn Tajana Ries Stefan Söllner Janina Müller-Deile Maike Büttner-Herold Kerstin Amann Christoph Daniel
author_facet	Eva Vonbrunn Tajana Ries Stefan Söllner Janina Müller-Deile Maike Büttner-Herold Kerstin Amann Christoph Daniel
author_sort	Eva Vonbrunn
title	Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
title_short	Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
title_full	Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
title_fullStr	Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
title_full_unstemmed	Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
title_sort	multiplex gene analysis reveals t-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/42e35ca04e0d403eb6a67e41362a8977
work_keys_str_mv	AT evavonbrunn multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT tajanaries multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT stefansollner multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT janinamullerdeile multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT maikebuttnerherold multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT kerstinamann multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants AT christophdaniel multiplexgeneanalysisrevealstcellandantibodymediatedrejectionspecificupregulationofcomplementinrenaltransplants
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Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants

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