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-IFN-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 the factors underlying the anti-IFN-beta antibody response should accelerate the engineering of less immunogenic IFN-beta therapeutics.
Barbosa
Maria D F S
MD
Xencor, Inc., 111 W. Lemon Avenue, Monrovia, CA 91016, USA. mbarbosa@xencor.com
Vielmetter
Jost
J
Chu
Seung
S
Smith
David D
DD
Jacinto
Jonathan
J
D000906:Antibodies / Q000097:blood*; D005802:Genes, MHC Class II / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000097:blood* / Q000276:immunology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000276:immunology*; D010361:Patients; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C456920:HLA-DRB1*07 antigen; D000068576:Interferon beta-1b; D016899:Interferon-beta