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Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors
JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761562/ https://www.ncbi.nlm.nih.gov/pubmed/33276614 http://dx.doi.org/10.3390/v12121380 |
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author | Solis, Morgane Guffroy, Aurélien Lersy, François Soulier, Eric Gallais, Floriane Renaud, Mathilde Douiri, Nawal Argemi, Xavier Hansmann, Yves De Sèze, Jérôme Kremer, Stéphane Fafi-Kremer, Samira |
author_facet | Solis, Morgane Guffroy, Aurélien Lersy, François Soulier, Eric Gallais, Floriane Renaud, Mathilde Douiri, Nawal Argemi, Xavier Hansmann, Yves De Sèze, Jérôme Kremer, Stéphane Fafi-Kremer, Samira |
author_sort | Solis, Morgane |
collection | PubMed |
description | JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF. |
format | Online Article Text |
id | pubmed-7761562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77615622020-12-26 Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors Solis, Morgane Guffroy, Aurélien Lersy, François Soulier, Eric Gallais, Floriane Renaud, Mathilde Douiri, Nawal Argemi, Xavier Hansmann, Yves De Sèze, Jérôme Kremer, Stéphane Fafi-Kremer, Samira Viruses Communication JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF. MDPI 2020-12-02 /pmc/articles/PMC7761562/ /pubmed/33276614 http://dx.doi.org/10.3390/v12121380 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Solis, Morgane Guffroy, Aurélien Lersy, François Soulier, Eric Gallais, Floriane Renaud, Mathilde Douiri, Nawal Argemi, Xavier Hansmann, Yves De Sèze, Jérôme Kremer, Stéphane Fafi-Kremer, Samira Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title | Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title_full | Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title_fullStr | Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title_full_unstemmed | Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title_short | Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors |
title_sort | inadequate immune humoral response against jc virus in progressive multifocal leukoencephalopathy non-survivors |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761562/ https://www.ncbi.nlm.nih.gov/pubmed/33276614 http://dx.doi.org/10.3390/v12121380 |
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