Infection with JC virus (JCV) is not noticeable and is usually inconsequential. Natalizumab therapy, however, blocks the very late antigen-4 adhesion molecule on immune cells, preventing them from attaching to vascular cell adhesion molecule-1 on brain endothelial cells and then penetrating into the CNS. The dearth of T cells, and perhaps other factors, allows JCV to infect oligodendroglia and cause progressive multifocal leukoencephalopathy (PML), at a risk of 1/1,000 per year. In this issue of Neurology® Neuroimmunology & Neuroinflammation, Schwab et al.1 find that natalizumab markedly increases levels of the JCV antibodies that may foretell the risk of PML.
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