Inter- and intralaboratory comparison of JC polyomavirus antibody testing using two different virus-like particle-based assays

Piotr Kardas, Mohammadreza Sadeghi, Fabian H. Weissbach, Tingting Chen, Lea Hedman, Eeva Auvinen, Klaus Hedman, Hans H. Hirsch

Research output: Contribution to journalArticle

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Abstract

JC polyomavirus (JCPyV) can cause progressive multifocal leukoencephalopathy (PML), a debilitating, often fatal brain disease in immunocompromised patients. JCPyV-seropositive multiple sclerosis (MS) patients treated with natalizumab have a 2- to 10-fold increased risk of developing PML. Therefore, JCPyV serology has been recommended for PML risk stratification. However, different antibody tests may not be equivalent. To study intra- and interlaboratory variability, sera from 398 healthy blood donors were compared in 4 independent enzyme-linked immunoassay (ELISA) measurements generating >1,592 data points. Three data sets (Basel1, Basel2, and Basel3) used the same basic protocol but different JCPyV virus-like particle (VLP) preparations and introduced normalization to a reference serum. The data sets were also compared with an independent method using biotinylated VLPs (Helsinki1). VLP preadsorption reducing ≥35% activity was used to identify seropositive sera. The results indicated that Basel1, Basel2, Basel3, and Helsinki1 were similar regarding overall data distribution (P = 0.79) and seroprevalence (58.0, 54.5, 54.8, and 53.5%, respectively; P = 0.95). However, intra-assay intralaboratory comparison yielded 3.7% to 12% discordant results, most of which were close to the cutoff (0.080 < optical density [OD] < 0.250) according to Bland-Altman analysis. Introduction of normalization improved overall performance and reduced discordance. The interlaboratory interassay comparison between Basel3 and Helsinki1 revealed only 15 discordant results, 14 (93%) of which were close to the cutoff. Preadsorption identified specificities of 99.44% and 97.78% and sensitivities of 99.54% and 95.87% for Basel3 and Helsinki1, respectively. Thus, normalization to a preferably WHO-approved reference serum, duplicate testing, and preadsorption for samples around the cutoff may be necessary for reliable JCPyV serology and PML risk stratification.

Original languageEnglish (US)
Pages (from-to)1581-1588
Number of pages8
JournalClinical and Vaccine Immunology
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

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JC Virus
Viruses
Virion
Progressive Multifocal Leukoencephalopathy
Assays
Antibodies
Testing
Density (optical)
Serology
Serum
Brain
Blood
Seroepidemiologic Studies
Immunocompromised Host
Brain Diseases
Enzymes
Blood Donors
Immunoenzyme Techniques
Multiple Sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Inter- and intralaboratory comparison of JC polyomavirus antibody testing using two different virus-like particle-based assays. / Kardas, Piotr; Sadeghi, Mohammadreza; Weissbach, Fabian H.; Chen, Tingting; Hedman, Lea; Auvinen, Eeva; Hedman, Klaus; Hirsch, Hans H.

In: Clinical and Vaccine Immunology, Vol. 21, No. 11, 01.11.2014, p. 1581-1588.

Research output: Contribution to journalArticle

Kardas, Piotr ; Sadeghi, Mohammadreza ; Weissbach, Fabian H. ; Chen, Tingting ; Hedman, Lea ; Auvinen, Eeva ; Hedman, Klaus ; Hirsch, Hans H. / Inter- and intralaboratory comparison of JC polyomavirus antibody testing using two different virus-like particle-based assays. In: Clinical and Vaccine Immunology. 2014 ; Vol. 21, No. 11. pp. 1581-1588.
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