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

Interferon-beta (IFN-beta) is currently the first-line therapy for the treatment of multiple sclerosis (MS). However, a significant percentage of MS patients develop anti-TFN-beta 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-beta antibody response. We identified IFN-beta 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-beta treated patients with the DRB1*0701 allele indicated a role for T-cell activation in IFN-beta immunogenicity. These results suggest that HLA typing of MS patients may provide an accurate screen for subjects who are likely to develop anti-IFN-beta antibodies and should therefore be considered for alternative therapies. In addition, elucidation of factors underlying the anti-IFN-beta antibody response should accelerate the engineering of less immunogenic IFN-beta therapeutics. (c) 2005 Elsevier Inc. All rights reserved.