title: The risk of progressive multifocal leukoencephalopathy under biological agents used in the treatment of chronic inflammatory diseases.
abstract: Biological agents such as monoclonal antibodies and soluble cytokine receptors have taken on an expanding role in the treatment of chronic immune mediated diseases. Progressive multifocal leukoencephalopathy (PML) is a rare central neurological disease caused by JC virus infection that has been described in the setting of conditions with severe impairment of immune surveillance, such as haematological malignancies, stem cell or solid organ transplantation and AIDS. This serious demyelinating disease has recently been described in patients receiving monoclonal antibodies for chronic inflammatory diseases such as multiple sclerosis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus or psoriasis. We review here the disease of PML, the different biological agents used in chronic inflammatory diseases that are associated with an increased risk of PML (natalizumab, rituximab, efalizumab and alemtuzumab), and the potential mechanisms that may explain the development of PML. Based on current knowledge of the biology of the JC virus and on the mechanisms of action of these biological agents, we discuss currently available tools that may be helpful in evaluating the risk of PML in this patient population.
authors.forename: Éric
authors.initials: É
authors.lastname: Toussirot
authors.affiliation: University Hospital of Besançon, Clinical Investigation Center for Biotherapy INSERM CIC-1431, Place St Jacques, 25000 Besançon, France. etoussirot@chu-besancon.fr.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Bereau
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001688:Biological Products / Q000009:adverse effects*; D002908:Chronic Disease; D006801:Humans; D016867:Immunocompromised Host; D007249:Inflammation / Q000188:drug therapy*; D007577:JC Virus / Q000187:drug effects / Q000276:immunology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D027601:Polyomavirus Infections / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D018570:Risk Assessment; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000139:chemically induced* / Q000276:immunology / Q000821:virology
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products