Measuring anti–JC virus antibody levels in cerebrospinal fluid may complement testing for viral DNA in cerebrospinal fluid and provide earlier detection of progressive multifocal leukoencephalopathy cases, according to the results of a retrospective case-control study of natalizumab-treated multiple sclerosis patients.
Cerebrospinal fluid (CSF) measurements of anti–JC virus (JCV) antibodies could help to identify patients with natalizumab (Tysabri)-associated progressive multifocal leukoencephalopathy (PML) who have repetitively undetectable levels of JC virus DNA in cerebrospinal fluid and often have levels less than 100 copies/mL at the time of PML diagnosis. Such measurements could help to avoid a delayed diagnosis or the need for brain biopsy to confirm the clinical suspicion of PML, said Dr. Clemens Warnke of the department of neurology at Heinrich-Heine-University, Düsseldorf, Germany, and his colleagues (Ann. Neurol. 2014 April 11 [doi:10.1002/ana.24153]).
The investigators compared serums and CSF samples taken from 37 multiple sclerosis patients with natalizumab-associated PML and 89 multiple sclerosis patients treated with natalizumab who did not have PML and calculated their cerebrospinal fluid JCV antibody index (AIJCV) as a measure of intrathecal synthesis of anti–JC virus antibodies. An AIJCV greater than 1.5 was observed in 26 (70%) of the 37 patients with natalizumab-associated PML, but not in any of the 89 control patients. In 20 patients with samples available from the time of diagnosis of natalizumab-associated PML, 11 (55%) had an AIJCV greater than 1.5. A total of 14 of the 20 patients had JC virus DNA levels less than 100 copies/mL, including 8 with an AIJCV greater than 1.5.
The calculation of an AIJCV greater than 1.5 – which provides clear evidence of intrathecal synthesis of anti-JCV antibodies – allowed the investigators to "exclude pure diffusion and disturbance of blood-CSF barrier function as a putative explanation of increased levels of anti-JCV antibodies in CSF in cases of PML."
The necessity of a lumbar puncture to determine the AIJCV – just as with screening CSF for JC virus DNA – makes the technique "unsuitable for PML risk prediction," but because other promising methods for risk prediction have not been prospectively validated, the investigators "propose the determination of the CSF AIJCV in addition to the JCV-DNA PCR [polymerase chain reaction] in CSF in cases of possible or probable PML (based on clinical, MRI-, and/or JCV-DNA PCR findings) in patients at risk."
The investigators’ work was supported by various sources, including grants from Heinrich-Heine University, the German Ministry for Education and Research, and the Innovative Medicines Initiative Joint Undertaking within the European Union’s Seventh Framework Program, as well as a fellowship stipend from the European Committee for Treatment and Research in MS.