Anti‐JC virus antibodies: Implications for PML Risk Stratification

Abstract

This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML.

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

“…In the aforementioned study, one patient tested positive for the antibodies 2 months before PML diagnosis. This patient had tested negative for anti-JCV antibodies 15 months prior to PML diagnosis [67], indicating either exposure to JCV at some point between the two tests or that seroconversion is possible even in individuals who are anti-JCV antibody negative; it is estimated that patients seroconvert at a rate of 1%-2% per annum, prompting some clinicians to recommend biannual JCV antibody testing in anti-JCV antibodynegative patients [74]. Furthermore, a recent study of 200 patients with MS found that approximately 5% of those with undetectable anti-JCV antibodies in serum had high anti-JCV antibody values in cerebrospinal fluid, showing that levels of these antibodies in the two locations do not always correlate [75].…”

Use of Natalizumab in Patients with Multiple Sclerosis: 2015 Update

“…The overall JCV-positivity rates with this assay have ranged from approximately 50% to 60%. [20][21][22][23] Since this index was introduced, we no longer simply consider a patient's JCV serostatus, but also take into account the magnitude of positivity. Subjects with higher anti-JCV antibody indices are at higher risk of PML than JCV-positive patients with lower indices.…”

“…24 Note that there is a false-negative rate of approximately 2.0% to 2.5% per year, and seroconversion occurs in approximately 2% to 8% of natalizumab-treated patients per year. 20,21 It is also important to note that there can be fluctuation in the JCV index at lower levels. Table 2 shows the panel's recommendations for natalizumab therapy depending on these three risk factors.…”

Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy

“…However, at present, there is no blood biomarker of JCV activity that can be used alone to diagnose PML, and a failure to detect JCV DNA in the cerebrospinal fluid (CSF) does not rule out the possibility of having PML, particularly in the earlier stages of the disease (Brew et al, 2010;Cordioli et al, 2014). The only humoral parameter obtained routinely is the JCV seropositivity status, which is evaluated by detecting antibodies directed against JCV VP1 (the main surface JCV protein) using the single validated STRATIFY JC virus™ assay (Gorelik et al, 2010;Bozic et al, 2011;Lee et al, 2013).This assay allows neurologists to detect patients at higher risk of developing PML. In particular, three factors-the presence of anti-JCV antibodies, with a lower risk of developing PML in patients with low antibody titers , previous use of immunosuppressants, and protracted duration of treatment, especially if longer than 2 years-seem to contribute to the overall risk of natalizumab-associated PML .…”