遗传因素在第九凝血因子的免疫原性的治疗血友病B。
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赛,Hamasaki-Katagiri N, Pandey GS, Yanover C, Guelcher C, Simhadri六世,Dandekar年代,格雷拉MF, Kimchi-Sarfaty C,桑拿泽
遗传因素在第九凝血因子的免疫原性的治疗血友病B。
血友病。2015年3月,21 (2):210 - 8。doi: 10.1111 / hae.12553。Epub 2014 12月2。
- PubMed ID
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25470321 (在PubMed]
- 文摘
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抑制剂是一个障碍血友病B的有效管理(HB),但有有限的理解潜在的遗传风险因子。在这项研究中,我们的目标是理解F9基因突变的作用抑制剂开发HB患者。F9基因的突变被发现,HLA输入执行五个男孩严重HB。CDC血友病B的数据变异项目(CHBMP)数据库被用来评估F9基因突变类型和抑制剂发展之间的联系。CHBMP数据库的分析表明,大中断F9基因与抑制剂的终生患病率更高。我们发现以下突变五个主题,包括四个小说突变:废话3例(c。223 C > T;p。Arg75 *两兄弟姐妹,c。553 C > T;p.Glu185 *);插接在两个病人(c。723 + 1 G > A, c。278 - 27 > G); Missense in one patient (c.580 A>G, p.Thr194Ala; c.723 G>T; p.Gln241His). Of the two siblings only one responded to immune tolerance induction (ITI). These siblings have identical F9 gene mutations but differ with respect to the HLA alleles. Interestingly, an analysis of peptide-MHC binding affinities shows a significantly higher (one-sided unpaired t-test, P = 0.0018) median affinity for FIX-derived peptides in the sibling that responded to ITI. We conclude that the nature of the F9 gene mutation may be an important risk factor for the development of inhibitors. In addition, the HLA alleles of the individual patients, in conjunction with the mutation type, could be a predictor for the development of inhibitors as well as the response to ITI.