Clinical link between MHC class II haplotype and interferon-beta (IFN-β) immunogenicity
Clinical link between MHC class II haplotype and interferon-beta (IFN-β) immunogenicity
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DOI：
10.1016/j.clim.2005.08.017
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发表时间：
2006-01-01
影响因子：
8.6
通讯作者：
Jacinto, J
中科院分区：
文献类型：
--
作者：
Barbosa, MDFS;Vielmetter, J;Jacinto, J
干扰素-β（IFN-β）目前是治疗多发性硬化症（MS）的一线疗法。然而，很大一部分多发性硬化症患者会产生抗 TFN-β 抗体，这会降低药物的疗效。我们描述了 23% 的研究患者中存在的常见 MHC II 类等位基因 (DRB1*0701) 与抗 IFN-β 抗体反应之间的关联。我们使用表达该等位基因的 B 细胞系进行肽结合测定，鉴定了 IFN-β 表位。此外，使用来自 IFN-β 治疗的 DRB1*0701 等位基因患者的外周血单核细胞 (PBMC) 获得的表位特异性激活反应表明 T 细胞激活在 IFN-β 免疫原性中发挥作用。这些结果表明，多发性硬化症患者的 HLA 分型可以为可能产生抗 IFN-β 抗体的受试者提供准确的筛查，因此应考虑采用替代疗法。此外，阐明抗 IFN-β 抗体反应的潜在因素应该会加速免疫原性较低的 IFN-β 疗法的工程设计。 (c) 2005 Elsevier Inc. 保留所有权利。
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.