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1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients

BACKGROUND: Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivation and associated complications in both solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Reliably assessing CMV-CMI is desirable to...

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Autores principales: Banas, Bernhard, Steubl, Dominik, Renders, Lutz, Chittka, Dominik, Banas, Miriam, Wekerle, Thomas, Koch, Martina, Witzke, Oliver, Lindemann, Monika, Muehlfeld, Anja, Sommerer, Claudia, Habicht, Antja, Hugo, Christian, Huenig, Thomas, Mielke, Stephan, Schreder, Martin, Wagner, Eva, Teschner, Daniel, Klein, Stefan, Heidenreich, Daniela, Kreil, Sebastian, Schaefer-Eckart, Kerstin, Gaertner, Johannes, Verbeek, Mareike, Grass, Sandra, Wolschke, Christine, Janson, Dietlinde, Kobbe, Guido, Kondakci, Mustafa, Ditschkowski, Markus, Gromke, Tanja, Hilgendorf, Inken, Lilienfeld-Toal, Marie Von, Schmidt, Traudel, Rascle, Anne, Barabas, Sascha, Deml, Ludwig, Wagner, Ralf, Kraemer, Bernhard, Krueger, Bernd, Wolff, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252655/
http://dx.doi.org/10.1093/ofid/ofy210.1403
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author Banas, Bernhard
Steubl, Dominik
Renders, Lutz
Chittka, Dominik
Banas, Miriam
Wekerle, Thomas
Koch, Martina
Witzke, Oliver
Lindemann, Monika
Muehlfeld, Anja
Sommerer, Claudia
Habicht, Antja
Hugo, Christian
Huenig, Thomas
Mielke, Stephan
Schreder, Martin
Wagner, Eva
Teschner, Daniel
Klein, Stefan
Heidenreich, Daniela
Kreil, Sebastian
Schaefer-Eckart, Kerstin
Gaertner, Johannes
Verbeek, Mareike
Grass, Sandra
Wolschke, Christine
Janson, Dietlinde
Kobbe, Guido
Kondakci, Mustafa
Ditschkowski, Markus
Gromke, Tanja
Hilgendorf, Inken
Lilienfeld-Toal, Marie Von
Schmidt, Traudel
Rascle, Anne
Barabas, Sascha
Deml, Ludwig
Wagner, Ralf
Kraemer, Bernhard
Krueger, Bernd
Wolff, Daniel
author_facet Banas, Bernhard
Steubl, Dominik
Renders, Lutz
Chittka, Dominik
Banas, Miriam
Wekerle, Thomas
Koch, Martina
Witzke, Oliver
Lindemann, Monika
Muehlfeld, Anja
Sommerer, Claudia
Habicht, Antja
Hugo, Christian
Huenig, Thomas
Mielke, Stephan
Schreder, Martin
Wagner, Eva
Teschner, Daniel
Klein, Stefan
Heidenreich, Daniela
Kreil, Sebastian
Schaefer-Eckart, Kerstin
Gaertner, Johannes
Verbeek, Mareike
Grass, Sandra
Wolschke, Christine
Janson, Dietlinde
Kobbe, Guido
Kondakci, Mustafa
Ditschkowski, Markus
Gromke, Tanja
Hilgendorf, Inken
Lilienfeld-Toal, Marie Von
Schmidt, Traudel
Rascle, Anne
Barabas, Sascha
Deml, Ludwig
Wagner, Ralf
Kraemer, Bernhard
Krueger, Bernd
Wolff, Daniel
author_sort Banas, Bernhard
collection PubMed
description BACKGROUND: Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivation and associated complications in both solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. We demonstrate here the suitability of a novel IFN-γ ELISpot assay (T-Track(®) CMV), based on the stimulation of PBMC with pp65 and IE-1 CMV proteins, to monitor CMV-CMI in SOT and HSCT patients. METHODS: Two independent prospective, longitudinal, observational, multicenter studies were conducted: in 86 intermediate-risk (D−/R+, D+/R+) renal transplant recipients (completed), and in 175 intermediate- or high-risk (D+/R+, D+/R−, D−/R+) HSCT recipients (ongoing). In both studies, patients underwent pre-emptive antiviral therapy. CMV-CMI, CMV load and clinical complications were monitored over ~6 months post-transplantation. RESULTS: In the kidney transplantation setting, 95% and 88–92% of IFN-γ ELISpot test results were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive therapy and increased in patients with graft rejection, indicating the ability of the assay to monitor the patients’ immunosuppressive state. Interestingly, median pp65-specific response was 9-fold higher in patients with self-clearing viral load compared with antivirally-treated patients prior to first detection of CMV (MWU; P < 0.001), suggesting that reactivity to pp65 is a potential immunocompetence marker. In HSCT patients, interim data analysis indicates that pp65-specific CMI measured after resolution of a primary CMV reactivation (requiring antiviral treatment) is a fair predictor of occurrence of recurrent CMV reactivation. Out of 71 patients (25 D+/R+, 3 D+/R−, 43 D−/R+) who experienced a primary CMV reactivation, 27 encountered a recurrent CMV reactivation. Interestingly, 39/44 (89%) patients free of recurrent reactivation had a positive pp65-specific test result following primary CMV reactivation. CONCLUSION: Altogether, this novel IFN-γ ELISpot assay is a highly sensitive immune-monitoring tool with a potential use for the risk assessment of CMV-related clinical complications after SOT and HSCT. DISCLOSURES: All authors, Lophius Biosciences: Investigator, Research support.
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spelling pubmed-62526552018-11-28 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients Banas, Bernhard Steubl, Dominik Renders, Lutz Chittka, Dominik Banas, Miriam Wekerle, Thomas Koch, Martina Witzke, Oliver Lindemann, Monika Muehlfeld, Anja Sommerer, Claudia Habicht, Antja Hugo, Christian Huenig, Thomas Mielke, Stephan Schreder, Martin Wagner, Eva Teschner, Daniel Klein, Stefan Heidenreich, Daniela Kreil, Sebastian Schaefer-Eckart, Kerstin Gaertner, Johannes Verbeek, Mareike Grass, Sandra Wolschke, Christine Janson, Dietlinde Kobbe, Guido Kondakci, Mustafa Ditschkowski, Markus Gromke, Tanja Hilgendorf, Inken Lilienfeld-Toal, Marie Von Schmidt, Traudel Rascle, Anne Barabas, Sascha Deml, Ludwig Wagner, Ralf Kraemer, Bernhard Krueger, Bernd Wolff, Daniel Open Forum Infect Dis Abstracts BACKGROUND: Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivation and associated complications in both solid-organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. We demonstrate here the suitability of a novel IFN-γ ELISpot assay (T-Track(®) CMV), based on the stimulation of PBMC with pp65 and IE-1 CMV proteins, to monitor CMV-CMI in SOT and HSCT patients. METHODS: Two independent prospective, longitudinal, observational, multicenter studies were conducted: in 86 intermediate-risk (D−/R+, D+/R+) renal transplant recipients (completed), and in 175 intermediate- or high-risk (D+/R+, D+/R−, D−/R+) HSCT recipients (ongoing). In both studies, patients underwent pre-emptive antiviral therapy. CMV-CMI, CMV load and clinical complications were monitored over ~6 months post-transplantation. RESULTS: In the kidney transplantation setting, 95% and 88–92% of IFN-γ ELISpot test results were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive therapy and increased in patients with graft rejection, indicating the ability of the assay to monitor the patients’ immunosuppressive state. Interestingly, median pp65-specific response was 9-fold higher in patients with self-clearing viral load compared with antivirally-treated patients prior to first detection of CMV (MWU; P < 0.001), suggesting that reactivity to pp65 is a potential immunocompetence marker. In HSCT patients, interim data analysis indicates that pp65-specific CMI measured after resolution of a primary CMV reactivation (requiring antiviral treatment) is a fair predictor of occurrence of recurrent CMV reactivation. Out of 71 patients (25 D+/R+, 3 D+/R−, 43 D−/R+) who experienced a primary CMV reactivation, 27 encountered a recurrent CMV reactivation. Interestingly, 39/44 (89%) patients free of recurrent reactivation had a positive pp65-specific test result following primary CMV reactivation. CONCLUSION: Altogether, this novel IFN-γ ELISpot assay is a highly sensitive immune-monitoring tool with a potential use for the risk assessment of CMV-related clinical complications after SOT and HSCT. DISCLOSURES: All authors, Lophius Biosciences: Investigator, Research support. Oxford University Press 2018-11-26 /pmc/articles/PMC6252655/ http://dx.doi.org/10.1093/ofid/ofy210.1403 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Banas, Bernhard
Steubl, Dominik
Renders, Lutz
Chittka, Dominik
Banas, Miriam
Wekerle, Thomas
Koch, Martina
Witzke, Oliver
Lindemann, Monika
Muehlfeld, Anja
Sommerer, Claudia
Habicht, Antja
Hugo, Christian
Huenig, Thomas
Mielke, Stephan
Schreder, Martin
Wagner, Eva
Teschner, Daniel
Klein, Stefan
Heidenreich, Daniela
Kreil, Sebastian
Schaefer-Eckart, Kerstin
Gaertner, Johannes
Verbeek, Mareike
Grass, Sandra
Wolschke, Christine
Janson, Dietlinde
Kobbe, Guido
Kondakci, Mustafa
Ditschkowski, Markus
Gromke, Tanja
Hilgendorf, Inken
Lilienfeld-Toal, Marie Von
Schmidt, Traudel
Rascle, Anne
Barabas, Sascha
Deml, Ludwig
Wagner, Ralf
Kraemer, Bernhard
Krueger, Bernd
Wolff, Daniel
1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title_full 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title_fullStr 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title_full_unstemmed 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title_short 1575. Clinical Validation of a Novel ELISpot-based in vitro Diagnostic Assay to Monitor CMV-Specific Cell-Mediated Immunity in SOT and HSCT Immunocompromised Patients
title_sort 1575. clinical validation of a novel elispot-based in vitro diagnostic assay to monitor cmv-specific cell-mediated immunity in sot and hsct immunocompromised patients
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252655/
http://dx.doi.org/10.1093/ofid/ofy210.1403
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