Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

PLoS One. 2017 Mar 20;12(3):e0174005. doi: 10.1371/journal.pone.0174005. eCollection 2017.

Abstract

Background: Risk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies.

Objective: To investigate the longitudinal evolution of anti-JCV antibody index and to determine the predictive value of baseline anti-JCV antibody index for long-term stability of anti-JCV antibody status.

Methods: MS patients from the MS centre of Medical University of Innsbruck, who had serum sampling for a time period of 4-6 years at intervals of 6±3 months, were included in this retrospective, longitudinal study. Anti-JCV antibody serological status and index were determined by 2-step second-generation anti-JCV antibody assay.

Results: 154 patients were included in this study. Median follow-up time was 63.7 months, with median 11 samples available per patient. At baseline, 111 (72.1%) patients were anti-JCV antibody positive. Baseline anti-JCV antibody index significantly correlated with age (R = 0.22, p = 0.005); there was no difference with respect to sex, disease duration or previously used disease-modifying treatment. During follow-up anti-JCV antibody status changed from negative to positive or vice versa in 17% of patients. In seronegative patients at baseline, baseline anti-JCV antibody index was significantly lower in those remaining seronegative at follow-up compared to those converting to seropositivity (median 0.16 vs. 0.24, p = 0.002). In seropositive patients at baseline, index was higher in those remaining seropositive compared to those reverting to seronegativity (2.6 vs. 0.45, p<10-7). Baseline anti-JCV antibody index >0.90 predicted stable positive serostatus (sensitivity 88.7%, specificity 96.5%) and <0.20 stable negative serostatus (sensitivity 61.3%, specificity 97.6%).

Conclusions: Anti-JCV antibody index remained relatively stable over 6-year follow-up with annual serostatus change of ~3%. Baseline anti-JCV antibody index predicted stable negative and stable positive JCV serostatus.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Antibodies, Viral / drug effects
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / therapeutic use
  • JC Virus / immunology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / virology
  • Natalizumab / therapeutic use
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Seroconversion / drug effects
  • Young Adult

Substances

  • Antibodies, Viral
  • Immunologic Factors
  • Natalizumab

Grants and funding

The funder (Biogen) provided financial support (recipient TB) for the laboratory work (determination of anti-JCV antibody status and index). TP as an employee of the funder contributed to the analysis and interpretation of the data and revision of the manuscript for its intellectual content. The funder did not play a role in study design, data collection, decision to publish and preparation of the original draft. The specific roles of the authors are articulated in the author contributions section.