Progressive multifocal leukoencephalopathy diagnosed by amplification of JC virus-specific DNA from cerebrospinal fluid

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Abstract

Objective

To study the diagnostic sensitivity and specificity of polymerase chain reaction (PCR) for the non-invasive diagnosis of progressive multifocal leukoencephalopathy (PML) in HIV-1-infected individuals.

Design

Retrospective analysis of stored cerebrospinal fluid (CSF) samples by PCR of HIV-1-infected patients.

Methods

Results of the PCR analysis of the CSF of three AIDS patients with autopsy-proven PML were compared with the results in 15 neurologically asymptomatic HIV-1-infected patients and with 15 AIDS patients with other opportunistic infections of the central nervous system (CNS). A polyclonal antiserum to simian virus 40 (SV40) cross-reacting with JC virus (JCV) late antigens was used for immunocytochemical confirmation of the diagnosis. Two different primer pairs, one taken from the VP1/large T gene and the other from the large T gene, were used to amplify JCV-specific DNA sequences from CSF.

Results

Five CSF samples were analysed and JCV-specific DNA found in three patients with autopsy-proven PML. No JCV-specific DNA was detected in 47 CSF samples, including serial samples from 14 of the 30 non-PML patients. The diagnosis of PML was confirmed in all three cases by immunocytochemistry. Conclusion: PML can be diagnosed by PCR analysis of CSF. The sensitivity and specificity of the method depends on the sensitivity of the primers used for amplification. Using a primer pair from the large T gene, JCV-specific DNA was amplified in three cases with PML as early as the day of presentation with the first neurological symptom of PML.

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