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Clin Immunol. 2006 Jan;118(1):42-50. Epub 2005 Nov 2.

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

Author information

1
Xencor, Inc., 111 W. Lemon Avenue, Monrovia, CA 91016, USA. mbarbosa@xencor.com

Erratum in

  • Clin Immunol. 2006 May;119(2):226.

Abstract

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.

PMID:
16260183
DOI:
10.1016/j.clim.2005.08.017
[Indexed for MEDLINE]

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