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The JC virus antibody response in serum and cerebrospinal fluid in progressive multifocal leucoencephalopathy
W A Knowles1, R W Luxton, J F Hand
1Virus Reference Division, Central Public Health Laboratory, Colindale Avenue, London NW9 5HT, UK.
Background:
A clinical diagnosis of progressive multifocal leucoencephalopathy (PML) can be confirmed by histological or virological examination of brain material. Whilst a less invasive method is provided by the detection of JC DNA in cerebrospinal fluid (CSF), very few studies have been done to assess the value of JC virus (JCV) serology in PML diagnosis.
Objectives:
To study the JCV antibody response in the serum and CSF of PML patients.
Study Design:
A retrospective study was done using haemagglutination inhibition (HI), M-antibody capture radioimmunoassay (MACRIA) and JC-specific oligoclonal IgG banding on one or more sera and/or CSFs from 28 confirmed PML patients. Seventy-one serum and CSF samples were tested from patients with memory loss or dementia as a control group.
Results:
Twenty-seven PML patients (96%) had detectable JCV HI antibody in the serum, with titres ranging from 1 : 10 to > 1 : 20480, compared to 48 (68%) of the controls (P = <0.005). JCV IgM antibody was detected in the serum of 12/22 (55%) PML patients. JCV HI antibody was detected in the CSF in 12 of 18 (67%) PML patients, antibody index measurements being used to control for a possible breakdown of the blood-brain barrier. Intrathecal JCV antibody was not found in any control patient. Locally produced JCV-specific IgG bands were detected in the CSF of 7 PML patients tested, confirming the intrathecal origin and specificity of the HI antibody.
Conclusions:
The presence of intrathecal JCV antibody indicates active central nervous system infection with JC virus, and provides a useful diagnostic test for PML, with a sensitivity of 67% and a specificity of 100%. The absence of serum JCV antibody nearly always excludes a diagnosis of PML, but the titre of antibody, IgG or IgM, correlates with the underlying condition rather than the development of neurological symptoms.
Insights
Detecting JC virus (JCV) antibodies in cerebrospinal fluid (CSF) is a sensitive and specific diagnostic marker for progressive multifocal leukoencephalopathy (PML). This study highlights JCV serology
Area of Science:
- Neurology
- Virology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) diagnosis relies on invasive methods like brain biopsy.
- JC virus (JCV) DNA detection in CSF is less invasive but its serological markers for PML diagnosis are under-explored.
Purpose of the Study:
- To investigate the JC virus (JCV) antibody response in serum and cerebrospinal fluid (CSF) of PML patients.
- To assess the diagnostic utility of JCV serology in PML.
Main Methods:
- Retrospective analysis of serum and CSF samples from 28 confirmed PML patients and 71 controls.
- Utilized haemagglutination inhibition (HI), M-antibody capture radioimmunoassay (MACRIA), and JC-specific oligoclonal IgG banding.
Main Results:
- JCV HI antibodies were detected in 96% of PML patients' serum versus 68% of controls (P < 0.005).
- JCV HI antibodies were found in CSF of 67% of PML patients, with 100% specificity.
- Intrathecal JCV-specific IgG bands confirmed local antibody production in PML patients.
Conclusions:
- Intrathecal JCV antibody presence signifies active CNS infection and is a valuable diagnostic marker for PML.
- Absence of serum JCV antibody largely excludes PML diagnosis.
- Antibody titers correlate with the underlying condition, not neurological symptoms.
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