Progressive multi-focal leucoencephalopathy - driven from rarity to clinical mainstream by iatrogenic immunodeficiency

Abstract

Advances in immune-mediated targeted therapies have proved to be a double-edged sword for patients by highlighting the risk of iatrogenic infective complications. This has been exemplified by progressive multi-focal leucoencephalopathy (PML), a hitherto rare devastating viral infection of the brain caused by the neurotrophic JC polyoma virus. While PML achieved prominence during the first two decades of the HIV epidemic, effective anti-retroviral treatment and restitution of T cell function has led to PML being less prominent in this population. HIV infection as a predisposing factor has now been supplanted by T cell immunodeficiency induced by a range of immune-mediated therapies as a major cause of PML. This review focuses on PML in the context of therapeutic immunosuppression and encompasses therapeutic monoclonal antibodies, novel immunomodulatory agents such as Fingolimod and dimethyl fumarate, as well as emerging data on PML in primary immune deficiency.

Keywords: EAE/MS; cell trafficking; immunodeficiency diseases; neuroimmunology; viral.

Figure 1

Time trends in reports of progressive multifocal leucoencephalopathy (PML) on PubMed 1960‐2016.

Figure 2

Schematic flowchart of spread of JC virus in the body.

Figure 3

Schematic depiction of key aspects of the host immune response to JC virus.

Figure 4

Schematic depiction of antigenic target(s) of Efalizumab, Natalizumab and Vedolizumab.