Abstract | OBJECTIVE: METHODS: A 2-step assay for detecting and confirming the presence of anti-JCV antibodies in human serum and plasma was developed and demonstrated to be both sensitive and specific. ELISA cutpoints were statistically established using sera from >800 MS patients from natalizumab clinical studies. Subsequently, this assay was used to determine the presence of anti-JCV antibodies in natalizumab-treated PML patients where serum samples were collected 16-180 months prior to the diagnosis of PML. RESULTS: In our evaluation of natalizumab-treated MS patients, 53.6% tested positive for anti-JCV antibodies, with a 95% confidence interval of 49.9 to 57.3%. The false-negative rate of the ELISA was calculated to be approximately 2.5%, with an upper 1-sided confidence limit of 4.4%. Notably, we observed anti-JCV antibodies in all 17 available pre-PML sera samples, which was significantly different from the 53.6% seropositivity observed in the overall MS study population (p < 0.0001). INTERPRETATION: This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML.
|
Authors | Leonid Gorelik, Michaela Lerner, Sarah Bixler, Mary Crossman, Brian Schlain, Kenneth Simon, Amy Pace, Anne Cheung, Ling Ling Chen, Melissa Berman, Fairuz Zein, Ewa Wilson, Ted Yednock, Alfred Sandrock, Susan E Goelz, Meena Subramanyam |
Journal | Annals of neurology
(Ann Neurol)
Vol. 68
Issue 3
Pg. 295-303
(Sep 2010)
ISSN: 1531-8249 [Electronic] United States |
PMID | 20737510
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies, Anti-Idiotypic
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- DNA, Viral
- Natalizumab
|
Topics |
- Antibodies, Anti-Idiotypic
(therapeutic use)
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- DNA, Viral
(immunology)
- Enzyme-Linked Immunosorbent Assay
- Humans
- JC Virus
(immunology)
- Leukoencephalopathy, Progressive Multifocal
(diagnosis, immunology, therapy)
- Natalizumab
- Risk Factors
- Viral Load
(methods)
|