Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development
| Autor: | Dagmar Rudzki, Xavier Montalban, Antonio Bertolotto, Florian Deisenhammer, Finn Sellebjerg, Raija L.P. Lindberg, Matthias Mehling, Per Soelberg Sørensen, Michael Khalil, Michael Guger, G Giovanonni, Chris H. Polman, Joep Killestein, Simona Malucchi, Franz Schautzer, Alban Millonig, Harald Hegen, Martina Hoelzl, Manuel Comabella |
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| Přispěvatelé: | Neurology, NCA - Neuroinflamation |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Myxovirus Resistance Proteins Time Factors Drug resistance TNF-Related Apoptosis-Inducing Ligand Multiple Sclerosis Relapsing-Remitting Predictive Value of Tests Gene expression medicine Humans Immunologic Factors Prospective Studies Neutralizing antibody Clinically isolated syndrome biology business.industry Multiple sclerosis Interferon-beta Middle Aged medicine.disease Antibodies Neutralizing Chemokine CXCL10 Europe Titer Early Diagnosis Treatment Outcome Neurology Immunology biology.protein Biomarker (medicine) Female Neurology (clinical) Antibody business Biomarkers Demyelinating Diseases |
| Zdroj: | Multiple Sclerosis, 20(5), 577-587. SAGE Publications Ltd Hegen, H, Millonig, A, Bertolotto, A, Comabella, M, Giovanonni, G, Guger, M, Hoelzl, M, Khalil, M, Killestein, J, Lindberg, R, Malucchi, S, Mehling, M, Montalban, X, Polman, C H, Rudzki, D, Schautzer, F, Sellebjerg, F, Sorensen, P S & Deisenhammer, F 2014, ' Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development ', Multiple Sclerosis, vol. 20, no. 5, pp. 577-587 . https://doi.org/10.1177/1352458513503597 |
| ISSN: | 1352-4585 |
| DOI: | 10.1177/1352458513503597 |
| Popis: | Background: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6–18 months on therapy. Objectives: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. Methods: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. Results: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. Conclusions: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies. |
| Databáze: | OpenAIRE |
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