Characterization of anti-natalizumab antibodies in multiple sclerosis patients
| Autor: | Anna Fogdell-Hahn, Tomas Olsson, Robert Movérare, Carolina Holmén, Jan Hillert, Elin Engdahl, Malin Lundkvist |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Multiple Sclerosis Time Factors Adolescent Enzyme-Linked Immunosorbent Assay Antibodies Monoclonal Humanized Young Adult Natalizumab Predictive Value of Tests medicine Humans Serologic Tests Aged Sweden biology business.industry Multiple sclerosis Middle Aged medicine.disease Anti-Drug Antibody Treatment Outcome Immunoglobulin M Neurology Immunoglobulin G Immunology biology.protein Female Neurology (clinical) Antibody business Immunosuppressive Agents medicine.drug |
| Zdroj: | Multiple Sclerosis Journal. 19:757-764 |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458512462920 |
| Popis: | 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®. 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. |
| Databáze: | OpenAIRE |
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