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From the Department of Neurology (Dr. Koralnik) and the Division of Viral Pathogenesis (Drs. Koralnik, Boden, and Letvin, and V.X. Mai and C.I. Lord), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Dr. I.J. Koralnik, Department of Neurology, Research East, Room 120, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
OBJECTIVE: To determine the clinical value of JC virus (JCV) detection in various anatomic compartments for the diagnosis of progressive multifocal leukoencephalopathy (PML).
METHODS: CSF, peripheral blood mononuclear cells (PBMC), plasma, and urine samples were evaluated from HIV-infected and uninfected individuals. JCV DNA was detected by PCR and was quantified using a competitive PCR ELISA.
RESULTS: JCV DNA was detected in one-third of the urine samples, regardless of HIV serostatus or clinical evidence of PML. JCV DNA was detected in five of eight PBMC and three of seven plasma samples of HIV-positive PML patients, in 13 of 103 PBMC and 7 of 32 plasma samples of HIV-positive persons without PML, but in 0 of 18 PBMC and 0 of 13 plasma samples of HIV-negative control subjects. There was no correlation between the presence of JCV DNA in the PBMC and plasma, but the detection of JCV in either compartment was associated with low CD4+ lymphocyte counts. JCV DNA was not detected in the CSF of 27 of 27 HIV-negative persons and 64 of 65 HIV-positive persons without PML, but was found in the CSF of three of three HIV-negative immunosuppressed individuals and 10 of 11 HIV-positive individuals with clinical and radiologic evidence of PML, confirmed by biopsy in four of four tested patients. PBMC harbored 10 to 90 JCV copies/µg DNA, and the CSF of the PML patients contained 3.65 x 104 to 2.04 x 105 JCV copies/mL CSF.
CONCLUSIONS: JCV viruria was found as frequently in HIV-positive individuals as in control subjects, suggesting that its detection has no clinical value. JCV detection in the blood correlates with immunosuppression and not with PML. The presence of JCV in the CSF is highly sensitive and specific for PML, and a high CSF JC viral load was associated with poor clinical outcome in patients receiving antiretroviral therapy. JCV quantification in the CSF constitutes a potentially important tool for monitoring clinical PML treatment trials.
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