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Article

Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation

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Department of Hematology, Medical Oncology, and Pneumology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany
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Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Eppendorf, Hamburg, Germany
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Medizinische Klinik 5, Klinikum Nürnberg Nord, Paracelsus Medizinische Privatuniversität, 90419 Nürnberg, Germany
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Department of Medicine II, University Medical Center Würzburg, 97080 Würzburg, Germany
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Department of Laboratory Medicine, CAST, Karolinska Institutet and University Hospital, 17177 Stockholm, Sweden
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Department of Hematology, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany
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Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, 07747 Jena, Germany
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Department of Hematology and Oncology, UMM University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany
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Medical Department, Hematology and Oncology, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany
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Innere Klinik, Tumorforschung, University Hospital Essen, 45147 Essen, Germany
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Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Eppendorf, Hamburg, Germany
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Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany
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Lophius Biosciences, 93053 Regensburg, Germany
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Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, 93053 Regensburg, Germany
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Department of Internal Medicine III, Hematology and Oncology, University Medical Center Regensburg, 93053 Regensburg, Germany
*
Authors to whom correspondence should be addressed.
Current address: First Department of Medicine, Center for Oncology and Hematology, Wilhelminenspital, 1160 Vienna, Austria.
Current address: Department of General-, Visceral- and Transplantation Surgery, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.
Academic Editor: Eric Deconinck
Diagnostics 2021, 11(2), 312; https://doi.org/10.3390/diagnostics11020312
Received: 17 December 2020 / Revised: 11 February 2021 / Accepted: 12 February 2021 / Published: 15 February 2021
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8+ counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients. View Full-Text
Keywords: CMV; CMV-specific cellular immunity; hematopoietic stem cell transplantation; recall antigen; peptide; immune monitoring; IFN-γ ELISpot; T cells; antigen processing and presentation; immunosuppression CMV; CMV-specific cellular immunity; hematopoietic stem cell transplantation; recall antigen; peptide; immune monitoring; IFN-γ ELISpot; T cells; antigen processing and presentation; immunosuppression
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Figure 1

MDPI and ACS Style

Wagner-Drouet, E.; Teschner, D.; Wolschke, C.; Schäfer-Eckart, K.; Gärtner, J.; Mielke, S.; Schreder, M.; Kobbe, G.; Hilgendorf, I.; Klein, S.; Verbeek, M.; Ditschkowski, M.; Koch, M.; Lindemann, M.; Schmidt, T.; Rascle, A.; Barabas, S.; Deml, L.; Wagner, R.; Wolff, D. Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation. Diagnostics 2021, 11, 312. https://doi.org/10.3390/diagnostics11020312

AMA Style

Wagner-Drouet E, Teschner D, Wolschke C, Schäfer-Eckart K, Gärtner J, Mielke S, Schreder M, Kobbe G, Hilgendorf I, Klein S, Verbeek M, Ditschkowski M, Koch M, Lindemann M, Schmidt T, Rascle A, Barabas S, Deml L, Wagner R, Wolff D. Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation. Diagnostics. 2021; 11(2):312. https://doi.org/10.3390/diagnostics11020312

Chicago/Turabian Style

Wagner-Drouet, Eva, Daniel Teschner, Christine Wolschke, Kerstin Schäfer-Eckart, Johannes Gärtner, Stephan Mielke, Martin Schreder, Guido Kobbe, Inken Hilgendorf, Stefan Klein, Mareike Verbeek, Markus Ditschkowski, Martina Koch, Monika Lindemann, Traudel Schmidt, Anne Rascle, Sascha Barabas, Ludwig Deml, Ralf Wagner, and Daniel Wolff. 2021. "Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation" Diagnostics 11, no. 2: 312. https://doi.org/10.3390/diagnostics11020312

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