• Clemens Warnke, Ryan Ramanujam, Tatiana Plavina, Tomas Bergström, Susan Goelz, Meena Subramanyam, Ingrid Kockum, Afsar Rahbar, Bernd C Kieseier, Carolina Holmén, Tomas Olsson, Jan Hillert, and Anna Fogdell-Hahn.
• Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, , Stockholm, Sweden.
• J. Neurol. Neurosurg. Psychiatr.. 2013 Nov 1;84(11):1199-205.

BackgroundThe anti-JC virus (JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) for higher or lower risk of progressive multifocal leukoencephalopathy (PML).ObjectiveTo assess the potential utility of anti-JCV antibody levels for earlier diagnosis or prediction of PML.MethodsAn analytically validated antibody assay was used to determine serological status, normalised optical density values, and dilution titres for anti-JCV antibodies. The method was applied to stored sera of 1157 patients with MS including five cases of PML, all enrolled in the Swedish pharmacovigilance study for natalizumab (NAT). Anticytomegalovirus (CMV) and antivaricella-zoster (VZV) antibody levels served as controls.ResultsPrior to treatment with NAT, anti-JCV antibody levels were stable in the anti-JCV positive patients. During therapy, a slight decrease in anti-JCV and anti-VZV antibody levels, but not anti-CMV antibody levels, was observed. All five patients who developed PML showed a mild to moderate increase in anti-JCV antibody levels at time of PML diagnosis; pre-PML samples suggested that this increase might start already prior to diagnosis of PML.ConclusionsTreatment initiation with NAT may lead to a slight decrease in anti-JCV and anti-VZV antibody levels, suggestive of a mild suppressive effect of NAT on antibody levels. Our findings in five cases of PML demonstrate that the onset of PML can be accompanied by increasing anti-JCV antibodies in serum. Monitoring of anti-JCV antibody levels could potentially be used as a tool for prediction or earlier diagnosis of PML during NAT treatment for MS. Further studies are warranted.

40 keywords...

hide…