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Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab.

Abstract
The dramatic increase in the incidence of progressive multifocal leukoencephalopathy (PML) that occurred as a consequence of the AIDS pandemic and the recent association of PML with the administration of natalizumab, a monoclonal antibody to alpha4 integrin that blocks inflammatory cell entry into the brain, has stimulated a great deal of interest in this previously obscure viral demyelinating disease. The etiology of this disorder is JC virus (JCV), a polyoma virus, observed in 80% of the population worldwide. Seroepidemiological studies indicate that infection with this virus typically occurs before the age of 20 years. No primary illness owing to JCV infection has been recognized and the means of spread from person to person remains obscure. Following infection, the virus becomes latent in bone marrow, spleen, tonsils and other tissues. Periodically the virus reactivates during which time it can be demonstrated in circulating peripheral lymphocytes. The latter is significantly more commonly observed in immunosuppressed populations than that in normal subjects. Despite the large pool of people infected with JCV, PML remains a relatively rare disease. It is seldom observed in the absence of an underlying predisposing illness, typically one that results in impaired cellular immunity. A variety of factors are likely responsible for the unique increase in frequency of PML in HIV infection relative to other underling immunosuppressive disorders. Preliminary data suggests that natalizumab appears to distinctively predispose recipients to PML relative to other infectious complications. Studies in these populations will be invaluable in understanding the mechanisms of disease pathogenesis.
AuthorsJoseph R Berger, Sidney Houff
JournalNeurological research (Neurol Res) Vol. 28 Issue 3 Pg. 299-305 (Apr 2006) ISSN: 0161-6412 [Print] England
PMID16687057 (Publication Type: Journal Article, Review)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Integrin alpha4beta1
  • Natalizumab
Topics
  • Acquired Immunodeficiency Syndrome (complications)
  • Antibodies, Monoclonal (adverse effects)
  • Antibodies, Monoclonal, Humanized
  • Disease Progression
  • Humans
  • Immunosuppression Therapy
  • Integrin alpha4beta1 (immunology)
  • JC Virus (pathogenicity)
  • Leukoencephalopathy, Progressive Multifocal (epidemiology, etiology, pathology, virology)
  • Natalizumab

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