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Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome
Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensiv...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893202/ https://www.ncbi.nlm.nih.gov/pubmed/24454857 http://dx.doi.org/10.1371/journal.pone.0085387 |
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author | Loebel, Madlen Strohschein, Kristin Giannini, Carolin Koelsch, Uwe Bauer, Sandra Doebis, Cornelia Thomas, Sybill Unterwalder, Nadine von Baehr, Volker Reinke, Petra Knops, Michael Hanitsch, Leif G. Meisel, Christian Volk, Hans-Dieter Scheibenbogen, Carmen |
author_facet | Loebel, Madlen Strohschein, Kristin Giannini, Carolin Koelsch, Uwe Bauer, Sandra Doebis, Cornelia Thomas, Sybill Unterwalder, Nadine von Baehr, Volker Reinke, Petra Knops, Michael Hanitsch, Leif G. Meisel, Christian Volk, Hans-Dieter Scheibenbogen, Carmen |
author_sort | Loebel, Madlen |
collection | PubMed |
description | Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4(+) and CD8(+) T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication. Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS. |
format | Online Article Text |
id | pubmed-3893202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38932022014-01-21 Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome Loebel, Madlen Strohschein, Kristin Giannini, Carolin Koelsch, Uwe Bauer, Sandra Doebis, Cornelia Thomas, Sybill Unterwalder, Nadine von Baehr, Volker Reinke, Petra Knops, Michael Hanitsch, Leif G. Meisel, Christian Volk, Hans-Dieter Scheibenbogen, Carmen PLoS One Research Article Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4(+) and CD8(+) T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication. Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS. Public Library of Science 2014-01-15 /pmc/articles/PMC3893202/ /pubmed/24454857 http://dx.doi.org/10.1371/journal.pone.0085387 Text en © 2014 Loebel et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Loebel, Madlen Strohschein, Kristin Giannini, Carolin Koelsch, Uwe Bauer, Sandra Doebis, Cornelia Thomas, Sybill Unterwalder, Nadine von Baehr, Volker Reinke, Petra Knops, Michael Hanitsch, Leif G. Meisel, Christian Volk, Hans-Dieter Scheibenbogen, Carmen Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title | Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title_full | Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title_fullStr | Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title_full_unstemmed | Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title_short | Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome |
title_sort | deficient ebv-specific b- and t-cell response in patients with chronic fatigue syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893202/ https://www.ncbi.nlm.nih.gov/pubmed/24454857 http://dx.doi.org/10.1371/journal.pone.0085387 |
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