JC virus antibody status underestimates infection rates

Ann Neurol. 2013 Jul;74(1):84-90. doi: 10.1002/ana.23893. Epub 2013 Aug 6.


Objective: JC virus (JCV) seropositivity is a risk factor for progressive multifocal leukoencephalopathy (PML) in patients on natalizumab. Accordingly, the JCV serological antibody test is of paramount importance in determining disease risk.

Methods: We tested the accuracy of the JCV serum antibody test by comparing the results of JCV serology to JCV viruria and viremia in 67 patients enrolled in a single-center, retrospective cohort study. Bodily fluids (urine and blood) were assessed for JCV DNA by real time quantitative polymerase chain reaction 6 to 47 months (mean = 26.1 months) before JCV antibody testing. In 10 individuals, blood and urine samples were obtained on 2 separate occasions at 6-month intervals.

Results: Forty (59.7%) of the 67 patients were JCV seropositive. Of 27 JCV seronegative patients, 10 (37%) had JCV viruria. Urine JCV DNA copy numbers were significantly higher in the seropositive group (mean log copy number = 5.93, range = 1.85-9.21) than the seronegative group (mean log copy number = 2.41, range = 1.85-5.43; p = 0.0026). Considering all body fluid test results, 50 (74.6%) of the 67 patients were previously infected with JCV.

Interpretation: The false-negative rate of the JCV serology in this study was 37%; therefore, JCV serostatus does not appear to identify all patients infected with JCV. Thus, a negative JCV antibody result should not be conflated with absence of JCV infection. This discordance may be important in understanding JCV biology, risk for PML, and PML pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • DNA, Viral / metabolism
  • Female
  • Humans
  • JC Virus / genetics
  • JC Virus / metabolism*
  • Leukoencephalopathy, Progressive Multifocal / blood
  • Leukoencephalopathy, Progressive Multifocal / diagnosis*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Tumor Virus Infections*
  • Young Adult


  • Autoantibodies
  • DNA, Viral