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Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors
Morgane Solis1,2, Aurélien Guffroy3, François Lersy4
1Virology Laboratory, Strasbourg University Hospitals, 67000 Strasbourg, France.
Abstract:
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.
Insights
JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML). High neutralizing antibody (NAb) titers in plasma and cerebrospinal fluid (CSF) may indicate better survival outcomes for PML patients.
Area of Science:
- Neurovirology
- Immunology
- Infectious Diseases
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus (JCV) in immunocompromised individuals.
- Current PML management focuses on immune restoration, lacking specific antiviral treatments.
- Identifying prognostic markers is critical due to PML's high mortality rate.
Purpose of the Study:
- To investigate JC virus (JCV) strain compartmentalization and humoral neutralizing responses in progressive multifocal leukoencephalopathy (PML).
- To understand PML pathophysiology and identify potential markers for patient survival.
Main Methods:
- Analysis of JC virus (JCV) viral loads in cerebrospinal fluid (CSF), plasma, and urine from four PML patients.
- Measurement of neutralizing antibody (NAb) titers against autologous JCV strains in different bodily fluids.
- Comparison of NAb titers and viral loads between survivor and non-survivor patients.
Main Results:
- Cerebrospinal fluid (CSF) showed the highest viral loads; plasma had lower loads, and urine was mostly negative.
- Plasma exhibited the highest neutralizing antibody (NAb) titers, significantly higher than in CSF and urine.
- Lower plasma NAb titers were observed in non-survivor patients; the sole survivor showed increasing NAb titers over time.
Conclusions:
- The humoral neutralizing response against autologous JC virus (JCV) strains may influence progressive multifocal leukoencephalopathy (PML) outcomes.
- Survivors of PML may develop robust neutralizing antibody (NAb) responses in both plasma and cerebrospinal fluid (CSF).
- Further research into NAb dynamics could lead to novel prognostic markers for PML.
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