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

Clin Exp Immunol. 2017 Jun;188(3):342-352. doi: 10.1111/cei.12948. Epub 2017 Mar 27.

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.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Brain / virology
  • Disease Management
  • Humans
  • Iatrogenic Disease / epidemiology
  • Immunosuppression Therapy / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • JC Virus
  • Leukoencephalopathy, Progressive Multifocal / diagnosis*
  • Leukoencephalopathy, Progressive Multifocal / epidemiology*
  • Leukoencephalopathy, Progressive Multifocal / therapy*
  • Polyomavirus Infections / epidemiology*

Substances

  • Antibodies, Monoclonal
  • Immunosuppressive Agents