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使用人/猪杂交因子VIII分析因子VIII抑制剂。

Analysis of factor VIII inhibitors using hybrid human/porcine factor VIII.

作者信息

Lollar P

机构信息

Department of Medicine, Emory University, Atlanta, GA 30322, USA.

出版信息

Thromb Haemost. 1997 Jul;78(1):647-51.

PMID:9198232
Abstract

Recombinant hybrid human/porcine factor VIII molecules have been used to map a major determinant of the epitope recognized by human anti-factor VIII A2 domain inhibitory antibodies to a region bounded by human fVIII residues Arg484-Ile508. This approach is being used to characterize the C2 domain inhibitor epitope. The process of creating hybrid human/porcine factor VIII molecules to map inhibitor epitopes produces procoagulantly active fVIII with reduced reactivity with clinically significant factor VIII inhibitors. This suggests that it may be possible to develop of a hybrid human/porcine factor VIII that is useful in the management of hemophilia A and acquired hemophilia.

摘要

重组人/猪杂交因子VIII分子已被用于将人抗因子VIII A2结构域抑制性抗体识别的表位的主要决定簇定位到由人fVIII残基Arg484 - Ile508界定的区域。该方法正用于表征C2结构域抑制剂表位。创建人/猪杂交因子VIII分子以定位抑制剂表位的过程产生了促凝活性fVIII,其与临床上重要的因子VIII抑制剂的反应性降低。这表明有可能开发出一种对A型血友病和获得性血友病治疗有用的人/猪杂交因子VIII。

相似文献

1
Analysis of factor VIII inhibitors using hybrid human/porcine factor VIII.使用人/猪杂交因子VIII分析因子VIII抑制剂。
Thromb Haemost. 1997 Jul;78(1):647-51.
2
Mapping factor VIII inhibitor epitopes using hybrid human/porcine factor VIII molecules.利用人/猪杂交因子VIII分子绘制因子VIII抑制剂表位图谱。
Haematologica. 2000 Oct;85(10 Suppl):26-8; discussion 28-30.
3
Induction of human factor VIII inhibitors in rats by immunization with human recombinant factor VIII: a small animal model for humans with high responder inhibitor phenotype.通过用人重组凝血因子 VIII 免疫大鼠诱导产生人凝血因子 VIII 抑制剂:一种用于具有高反应性抑制剂表型人类的小动物模型。
Thromb Haemost. 1996 Feb;75(2):318-25.
4
Analysis of the human factor VIII A2 inhibitor epitope by alanine scanning mutagenesis.通过丙氨酸扫描诱变分析人凝血因子VIII A2抑制剂表位
J Biol Chem. 1997 Nov 28;272(48):30191-5. doi: 10.1074/jbc.272.48.30191.
5
Identification of plasma antibody epitopes and gene abnormalities in Japanese hemophilia A patients with factor VIII inhibitor.日本血友病A伴凝血因子VIII抑制物患者血浆抗体表位及基因异常的鉴定
Nagoya J Med Sci. 2000 May;63(1-2):25-39.
6
Residues 484-508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII.第484至508位氨基酸残基包含人凝血因子VIII A2结构域中抑制性表位的主要决定簇。
J Biol Chem. 1995 Jun 16;270(24):14505-9. doi: 10.1074/jbc.270.24.14505.
7
A factor VIII neutralizing monoclonal antibody and a human inhibitor alloantibody recognizing epitopes in the C2 domain inhibit factor VIII binding to von Willebrand factor and to phosphatidylserine.一种在C2结构域识别表位的VIII因子中和单克隆抗体和一种人抑制性同种抗体可抑制VIII因子与血管性血友病因子及磷脂酰丝氨酸的结合。
Thromb Haemost. 1993 Mar 1;69(3):240-6.
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Mapping of FVIII inhibitor epitopes using cellulose-bound synthetic peptide arrays.使用纤维素结合合成肽阵列对FVIII抑制剂表位进行图谱分析。
J Immunol Methods. 2006 Jan 20;308(1-2):90-100. doi: 10.1016/j.jim.2005.10.016. Epub 2005 Dec 5.
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Humoral immune responsiveness to a defined epitope on factor VIII before and after B cell ablation with rituximab.使用利妥昔单抗进行B细胞消融前后,对凝血因子VIII上特定表位的体液免疫反应性。
Mol Immunol. 2008 Nov;46(1):8-15. doi: 10.1016/j.molimm.2008.06.015. Epub 2008 Aug 19.
10
Human anti-factor VIII antibodies: epitope localization and inhibitory function.人抗凝血因子VIII抗体:表位定位与抑制功能
Vox Sang. 1996;70 Suppl 1:9-14.

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Mol Ther Methods Clin Dev. 2020 Oct 22;19:486-495. doi: 10.1016/j.omtm.2020.10.013. eCollection 2020 Dec 11.
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Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.抗药物抗体:预测、降低或逆转生物治疗性免疫原性的新方法
Antibodies (Basel). 2018 May 31;7(2):19. doi: 10.3390/antib7020019.
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Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors.
拓展针对因VIII因子抑制剂而变得复杂的血友病治疗的直系同源基因方法。
J Thromb Haemost. 2015 Jan;13(1):72-81. doi: 10.1111/jth.12755. Epub 2014 Nov 11.
4
Phenotypes of allo- and autoimmune antibody responses to FVIII characterized by surface plasmon resonance.应用表面等离子共振技术对 FVIII 同种及自身抗体反应的表型进行鉴定。
PLoS One. 2013 May 8;8(5):e61120. doi: 10.1371/journal.pone.0061120. Print 2013.
5
Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.凝血因子VIII对甲型血友病血浆中凝血酶生成的增强作用及抗体特异性抑制的特征分析
PLoS One. 2012;7(10):e48172. doi: 10.1371/journal.pone.0048172. Epub 2012 Oct 29.
6
Passive transfer of polyethylene glycol to liposomal-recombinant human FVIII enhances its efficacy in a murine model for hemophilia A.聚乙二醇向脂质体重组人FVIII的被动转移增强了其在甲型血友病小鼠模型中的疗效。
J Pharm Sci. 2008 Sep;97(9):3753-64. doi: 10.1002/jps.21266.
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Phosphatidylserine containing liposomes reduce immunogenicity of recombinant human factor VIII (rFVIII) in a murine model of hemophilia A.含磷脂酰丝氨酸的脂质体可降低血友病A小鼠模型中重组人凝血因子VIII(rFVIII)的免疫原性。
J Pharm Sci. 2008 Apr;97(4):1386-98. doi: 10.1002/jps.21102.
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Characterization of factor VIII inhibitors.凝血因子 VIII 抑制剂的特性描述。
Int J Hematol. 2006 Feb;83(2):109-18. doi: 10.1532/IJH97.05160.