Sage Journals: Discover world-class research

Abstract

Background:

The StratifyJCV® test is a qualitative assay to classify MS patients as anti-JC virus (JCV) antibody positive or negative. Quantification of anti-JCV antibody levels in serum and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients might add to the progressive multifocal leukoencephalopathy (PML) risk assessment.

Objective:

The objective of this study is to test sera of patients in a quantitative anti-JCV antibody assay, and to compare the results with preexisting data from the StratifyJCV® test.

Methods:

Sera of a total of 175 MS patients and matched non-MS-controls were tested for anti-JCV antibodies using glutathione S-transferase-tagged-VP1 as antigen. Antibody reactivity was quantified in arbitrary units using human immunoglobulin as standard.

Results:

The comparison of our assay with StratifyJCV® showed good inter-assay agreement (kappa 0.6), and strong correlation for antibody reactivity (r² = 0.94). Discordant samples had low-reactive positivity, and a higher proportion (13% vs. 4%) tested positive in the StratifyJCV® test only.

Conclusions:

The method presented is a tool for the reliable quantification of anti-JCV antibodies, which demonstrates good agreement with results from StratifyJCV®. In contrast to StratifyJCV®, we pre-adsorbed all of the sera with BK virus (BKV) VP1 protein to reduce cross-reactivity. This step may account for a higher species-specificity of our assay. As such, our assay might be a promising additional tool for PML risk assessment.

Keywords

Multiple sclerosis Tysabri JC virus progressive multifocal leukoencephalopathy BK virus

Get full access to this article

View all access options for this article.

References

Warnke

Menge

Hartung

. Natalizumab and progressive multifocal leukoencephalopathy: What are the causal factors and can it be avoided? Arch Neurol 2010; 67: 923–930.

Kappos

Bates

Edan

. Natalizumab treatment for multiple sclerosis: Updated recommendations for patient selection and monitoring. Lancet Neurol 2011; 10: 745–758.

Clifford

De Luca

Simpson

. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: Lessons from 28 cases. Lancet Neurol 2010; 9: 438–446.

Monaco

Major

. The link between VLA-4 and JC virus reactivation. Expert Rev Clin Immunol 2012; 8: 63–72.

Gorelik

Lerner

Bixler

. Anti-JC virus antibodies: Implications for PML risk stratification. Ann Neurol 2010; 68: 295–303.

Bozic

Richman

Plavina

. Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY-1. Ann Neurol 2011; 70: 713–721.

Warnke

Adams

Hartung

. Risk stratification of progressive multifocal leukoencephalopathy under natalizumab: Recommendations for JC virus serology [in German]. Nervenarzt 2011; 82: 1314–1319.

Bloomgren

Richman

Hotermans

. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366: 1870–1880.

Trampe

Hemmelmann

Stroet

. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology 2012; 78: 1736–1742.

10.

Warnke

Subramanyam

Bergström

. Anti-JC virus antibody titer changes during natalizumab treatment in a Swedish MS cohort. American Academy of Neurology, 64th annual meeting, New Orleans, LA, USA, 21–28 April 2012, poster P02139.

11.

Lee

P PT

Castro

Berman

. An enhanced ELISA for detection of anti-JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. 22nd annual meeting of the European Neurological Society, Prague, Czech Republic, 9–12 June 2012.

12.

Frisque

Nucleotide sequence of the region encompassing the JC virus origin of DNA replication. J Virol 1983; 46: 170–176.

13.

Randhawa

Viscidi

Carter

. Identification of species-specific and cross-reactive epitopes in human polyomavirus capsids using monoclonal antibodies. J Gen Virol 2009; 90: 634–639.

14.

Hamilton

Gravell

Major

Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus. J Clin Microbiol 2000; 38: 105–109.

15.

Stolt

Sasnauskas

Koskela

. Seroepidemiology of the human polyomaviruses. J Gen Virol 2003; 84: 1499–1504.

16.

Egli

Infanti

Dumoulin

. Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 2009; 199: 837–846.

17.

Plavina

Berman

Njenga

. Multi-site analytical validation of an assay to detect anti-JCV antibodies in human serum and plasma. J Clin Virol 2012; 53: 65–71.

18.

Kjaerheim

Roe

Waterboer

. Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples. Int J Cancer 2007; 120: 2459–2465.

19.

Sehr

Muller

Hopfl

. HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S-transferase. J Virol Methods 2002; 106: 61–70.

20.

Sehr

Zumbach

Pawlita

A generic capture ELISA for recombinant proteins fused to glutathione S-transferase: Validation for HPV serology. J Immunol Methods 2001; 253: 153–162.

21.

McDonald

Compston

Edan

. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121–127.

22.

Waterboer

Dondog

Michael

. Dried blood spot samples for seroepidemiology of infections with human papillomaviruses, Helicobacter pylori, hepatitis C virus, and JC virus. Cancer Epidemiol Biomarkers Prev 2012; 21: 287–293. Epub 6 December 2011.

23.

Lucas

Hughes

Lay

. Epstein-Barr virus and multiple sclerosis. J Neurol Neurosurg Psychiatry 2011; 82: 1142–1148.

24.

Knowles

Pipkin

Andrews

. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003; 71: 115–123.

25.

Antonsson

Green

Mallitt

. Prevalence and stability of antibodies to the BK and JC polyomaviruses: A long-term longitudinal study of Australians. J Gen Virol 2010; 91: 1849–1853.

26.

Kean

Rao

Wang

. Seroepidemiology of human polyomaviruses. PLoS Pathog 2009; 5: e1000363.

27.

Olsson

Hillert

Alfredsson

. Anti-JCV antibody prevalence in a Swedish cohort of MS patients and non-MS-controls. 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Gothenburg, Sweden, 13–16 October 2010.

28.

Sundqvist

Warnke

Khademi

. Genetic influence on anti-JC-virus antibody seropositivity in MS patients and controls. Poster presentation (P807), 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, Amsterdam, The Netherlands, 14 October 2011.

29.

Warnke

Dehmel

Posevitz-Fejfar

. Anti-JC-virus antibody prevalence in a German MS cohort. Mult Scler 2012; 18: 1054–1055.

30.

Viscidi

Rollison

Sondak

. Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus. Clin Vaccine Immunol 2011; 18: 1737–1743.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.04 MB

10.41 MB

15.92 MB

0.30 MB

An assay to quantify species-specific anti-JC virus antibody levels in MS patients

Abstract

Background:

Objective:

Methods:

Results:

Conclusions:

Keywords

Get full access to this article

References

Supplementary Material