Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials
| Autor: | Christoph Pohl, Beyond, Bertram Müller-Myhsok, M. S. Freedman, Dorothea Buck, Stuart D. Cook, Till M.F. Andlauer, Frederik Barkhof, Frank Weber, Hans-Peter Hartung, Giancarlo Comi, Karl Köchert, Mark Mühlau, Ludwig Kappos, Bernhard Hemmer, Xavier Montalban, Benefit Study Groups, Douglas Jeffery, Massimo Filippi, Gilles Edan, Wilmar Igl, Eva-Maria Wicklein, Barry G. W. Arnason |
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| Přispěvatelé: | Buck, Dorothea, Andlauer, Till FM, Igl, Wilmar, Wicklein, Eva-Maria, Mühlau, Mark, Weber, Frank, Köchert, Karl, Pohl, Christoph, Arnason, Barry, Comi, Giancarlo, Cook, Stuart, Filippi, Massimo, Hartung, Hans-Peter, Jeffery, Dougla, Kappos, Ludwig, Barkhof, Frederik, Edan, Gille, Freedman, Mark S, Montalbán, Xavier, Müller-Myhsok, Bertram, Hemmer, Bernhard, Radiology and nuclear medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Multiple Sclerosis Genome-wide association study Single-nucleotide polymorphism Human leukocyte antigen Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Multiple Sclerosis Relapsing-Remitting Genetic variation medicine Humans Immunologic Factors Multiple sclerosi 030212 general & internal medicine Prospective Studies Allele interferon beta HLA-DRB1 genome-wide association study business.industry Multiple sclerosis Middle Aged medicine.disease Antibodies Neutralizing anti-drug antibodie Neurology Genetic marker Immunology genetic variation Female Neurology (clinical) business 030217 neurology & neurosurgery Genome-Wide Association Study HLA-DRB1 Chains Interferon beta-1b |
| Zdroj: | MULTIPLE SCLEROSIS JOURNAL Buck, D, Andlauer, T F, Igl, W, Wicklein, E-M, Mühlau, M, Weber, F, Köchert, K, Pohl, C, Arnason, B, Comi, G, Cook, S, Filippi, M, Hartung, H-P, Jeffery, D, Kappos, L, Barkhof, F, Edan, G, Freedman, M S, Montalbán, X, Müller-Myhsok, B, Hemmer, B & BEYOND and BENEFIT Study Groups 2019, ' Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials ', Multiple Sclerosis, vol. 25, no. 4, pp. 565-573 . https://doi.org/10.1177/1352458518763089 Multiple Sclerosis, 25(4), 565-573. SAGE Publications Ltd |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458518763089 |
| Popis: | Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies. |
| Databáze: | OpenAIRE |
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