Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort

Neurology. 2012 May 29;78(22):1736-42. doi: 10.1212/WNL.0b013e3182583022. Epub 2012 May 16.

Abstract

Objective: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML).

Methods: This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010.

Results: Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML.

Conclusions: These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antibodies, Viral / blood*
  • Clinical Trials as Topic
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Germany / epidemiology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • JC Virus / immunology*
  • Leukoencephalopathy, Progressive Multifocal / diagnosis*
  • Leukoencephalopathy, Progressive Multifocal / epidemiology
  • Leukoencephalopathy, Progressive Multifocal / immunology
  • Leukoencephalopathy, Progressive Multifocal / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / virology*
  • Natalizumab
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Single-Blind Method

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Immunosuppressive Agents
  • Natalizumab