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Characterization of anti-natalizumab antibodies in multiple sclerosis patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
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2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 6, 757-764 p.Article in journal (Refereed) Published
Abstract [en]

Background: A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies. Objective: The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients. Methods: Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1-4 antibodies using ELISA and ImmunoCAP (R). Results: Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time. Conclusions: The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1-4 antibodies could be used to discriminate between transiently and persistently positive patients.

Place, publisher, year, edition, pages
2013. Vol. 19, no 6, 757-764 p.
Keyword [en]
Anti-drug antibody, natalizumab, multiple sclerosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-201807DOI: 10.1177/1352458512462920ISI: 000318637900010OAI: oai:DiVA.org:uu-201807DiVA: diva2:629492
Available from: 2013-06-17 Created: 2013-06-17 Last updated: 2017-12-06Bibliographically approved

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Moverare, Robert

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