Clinical link between MHC class II haplotype and interferon-beta (IFN-β) immunogenicity

Abstract Interferon-beta (IFN-β) is currently the first-line therapy for the treatment of multiple sclerosis (MS). However, a significant percentage of MS patients develop anti-IFN-β antibodies, which can reduce the efficacy of the drug. We describe an association between a common MHC class II allele (DRB1*0701), present in 23% of the patients studied, and the anti-IFN-β antibody response. We identified IFN-β epitopes using a peptide-binding assay with B cell lines expressing this allele. Moreover, epitope-specific activation responses obtained with peripheral blood mononuclear cells (PBMCs) from IFN-β treated patients with the DRB1*0701 allele indicated a role for T-cell activation in IFN-β immunogenicity. These results suggest that HLA typing of MS patients may provide an accurate screen for subjects who are likely to develop anti-IFN-β antibodies and should therefore be considered for alternative therapies. In addition, elucidation of the factors underlying the anti-IFN-β antibody response should accelerate the engineering of less immunogenic IFN-β therapeutics.