ArticleAmerican journal of human genetics2008
HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Guideline
- Comparative assessment of immunogenicity of recombinant insulin Aspart from BioGenomics and its originator NovoRapid® in adult patients with type 2 diabetes mellitus.Journal of endocrinological investigation · 2024Trial
- Immunogenicity of LY2963016 insulin glargine and Lantus® insulin glargine in Chinese patients with type 1 or type 2 diabetes mellitus.Diabetes, obesity & metabolism · 2022Trial
- Trial
- Trial
- Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta.Journal of neurology · 2010Trial
- Genetic Influences on Disease-Modifying Therapy Response in Multiple Sclerosis: Current Insights and Future Directions.Balkan medical journal · 2026Review
- Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A Case-Control Study.International journal of molecular sciences · 2023Article
- Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.JCI insight · 2023Article
- The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population.Frontiers in immunology · 2023Article
- Review
- Potential protective role of a NOD2 polymorphism in the susceptibility to multiple sclerosis is not associated with interferon therapy.Biomedical reports · 2021Article
- Effect of O-linked glycosylation on the antigenicity, cellular uptake and trafficking in dendritic cells of recombinant Ber e 1.PloS one · 2021Article
- Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS.BMC medicine · 2020Article
- Specificity of the T Cell Response to Protein Biopharmaceuticals.Frontiers in immunology · 2020Review
- Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ.Frontiers in immunology · 2020Article
- Correlation between antidrug antibodies, pre-existing antidrug reactivity, and immunogenetics (MHC class II alleles) in cynomolgus macaque.Immunogenetics · 2019Article
- Pharmacogenomics of Multiple Sclerosis: A Systematic Review.Frontiers in neurology · 2019Review
- Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases.Biologics : targets & therapy · 2018Article
- Modulating the immune system through nanotechnology.Seminars in immunology · 2017Review
Corrections and comments
- Erratum issuedHackermueller, Jorg [corrected to Hackermüller, Jörg]; Wasmuth, Ralf [corrected to Wassmuth, Ralf]
Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation of antibodies to interferon-beta (IFN-beta), a protein-based disease-modifying agent for multiple sclerosis (MS), is a problem in clinical practice. These antibodies may neutralize the biological effects of the protein drug, potentially decreasing its therapeutic effects. By high-resolution HLA class I and II typing we identified two HLA class II alleles associated with the development of antibodies to IFN-beta. In two independent continuous and binary-trait association studies, HLA-DRB1*0401 and HLA-DRB1*0408 (odds ratio: 5.15)--but not other HLA alleles--were strongly associated with the development of binding and neutralizing antibodies to IFN-beta. The associated HLA-DRB1*04 alleles differ from nonassociated HLA-DRB1*04 alleles by a glycine-to-valine substitution in position 86 of the epitope-binding alpha-helix of the HLA class II molecule. The peptide-binding motif of HLA-DRB1*0401 and *0408 might promote binding and presentation of an immunogenic peptide, which may eventually break T cell tolerance and facilitate antibody development to IFN-beta. In summary, we identified genetic factors determining the immunogenicity of IFN-beta, a protein-based disease-modifying agent for the treatment of MS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.