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抗凝血因子VIII自身抗体的异质性:针对凝血因子VIII凝血蛋白明显不同抗原决定簇的特异性差异。

Heterogeneity of autoantibodies to factor VIII: differences in specificity for apparently distinct antigenic determinants of factor VIII coagulant protein.

作者信息

Croissant M P, Zuzel M, Allain J P

出版信息

Blood. 1983 Jul;62(1):133-40.

PMID:6190519
Abstract

The interference of antibodies to factor VIII coagulant protein (VIII:C) of 9 nonhemophilic patients with the binding to factor VIII coagulant antigen (VIII:CAg) of a reference hemophilic 125I-Fab' reagent, used in a liquid phase VIII:CAg assay, was studied. The binding competition was estimated from immunoradiometric assay (IRMA) dose-response slope of VIII:CAg present in patient plasma, interference of antibodies with the 125I-Fab' binding to VIII:CAg in normal plasma, and the displacement of antibody from the complexes with VIII:CAg by the 125I Fab'. Antibody populations from three patients were studied in detail; in the VIII:CAg assay, two of them interfered with the 125I-Fab' binding, and one did not (patient 1). The formation of stable complexes between antibodies of each patient and VIII:CAg was demonstrated by protein-A-Sepharose adsorption. The 125I-Fab' binding to VIII:CAg-anti-VIII:CAg IgG complexes indicated that patient 1 antibodies and the 125I-Fab' recognized different antigenic determinants, whereas the other two patient antibodies and 125I-Fab' recognized closely related or identical VIII:CAg determinants. These results demonstrate an apparently selective recognition of at least two distinct VIII:CAg determinants by naturally occurring antibodies, suggesting a possibility of a wider use of these antibodies in studies of the structure and function of factor VIII.

摘要

研究了9名非血友病患者的抗体对凝血因子VIII(VIII:C)的干扰作用,这些抗体干扰了一种用于液相VIII:CAg检测的参考血友病125I-Fab’试剂与VIII:CAg的结合。通过患者血浆中VIII:CAg的免疫放射分析(IRMA)剂量反应斜率、抗体对正常血浆中125I-Fab’与VIII:CAg结合的干扰以及125I Fab’从VIII:CAg复合物中置换抗体,来估计结合竞争情况。对三名患者的抗体群体进行了详细研究;在VIII:CAg检测中,其中两名患者的抗体干扰了125I-Fab’的结合,一名患者的抗体未产生干扰(患者1)。通过蛋白A-琼脂糖吸附证明了每位患者的抗体与VIII:CAg之间形成了稳定的复合物。125I-Fab’与VIII:CAg-抗VIII:CAg IgG复合物的结合表明,患者1的抗体和125I-Fab’识别不同的抗原决定簇,而其他两名患者的抗体和125I-Fab’识别密切相关或相同的VIII:CAg决定簇。这些结果表明,天然抗体对至少两种不同的VIII:CAg决定簇具有明显的选择性识别,提示这些抗体在凝血因子VIII的结构和功能研究中可能有更广泛的应用。

相似文献

1
Heterogeneity of autoantibodies to factor VIII: differences in specificity for apparently distinct antigenic determinants of factor VIII coagulant protein.抗凝血因子VIII自身抗体的异质性:针对凝血因子VIII凝血蛋白明显不同抗原决定簇的特异性差异。
Blood. 1983 Jul;62(1):133-40.
2
Studies on the stability of factor VIII coagulant antigen (VIII:CAg) in the presence of VIII:C antibodies.在存在VIII:C抗体的情况下,对凝血因子VIII凝血抗原(VIII:CAg)稳定性的研究。
Br J Haematol. 1983 Jan;53(1):55-63. doi: 10.1111/j.1365-2141.1983.tb01986.x.
3
Immunoradiometric assay of factor VIII: coagulant antigen using four human antibodies. Study of 27 cases of haemophilia A.使用四种人源抗体的凝血因子VIII:凝血抗原免疫放射分析。对27例甲型血友病的研究。
Br J Haematol. 1981 Feb;47(2):269-82. doi: 10.1111/j.1365-2141.1981.tb02788.x.
4
Studies on a monoclonal antibody to human factor viii coagulant activity, with a description of a facile two-site factor VIII coagulant antigen assay.关于人凝血因子VIII促凝活性单克隆抗体的研究,以及一种简便的双位点因子VIII促凝抗原检测方法的描述。
J Lab Clin Med. 1983 May;101(5):793-805.
5
The effect of naturally occurring antibodies to factor VIII on an immunoradiometric assay for factor VIII coagulant antigen. Observation on a cross-reacting material-positive (CRM+) hemophiliac with a factor VIII inhibit.天然存在的抗凝血因子VIII抗体对凝血因子VIII凝血抗原免疫放射分析的影响。对一名存在因子VIII抑制物的交叉反应物质阳性(CRM+)血友病患者的观察。
J Lab Clin Med. 1981 Jan;97(1):65-71.
6
Simplified immunoradiometric assay for factor VIII coagulant antigen.凝血因子 VIII 凝血抗原的简易免疫放射分析
Br J Haematol. 1982 May;51(1):47-57. doi: 10.1111/j.1365-2141.1982.tb07288.x.
7
Analysis of factor VIII coagulant antigen in normal, thrombin-treated, and hemophilic plasma.正常血浆、凝血酶处理血浆和血友病血浆中凝血因子 VIII 促凝抗原分析。
Proc Natl Acad Sci U S A. 1981 Aug;78(8):5137-41. doi: 10.1073/pnas.78.8.5137.
8
Precipitating anti-VIII:C antibodies in two patients with haemophilia A.两名甲型血友病患者体内的 VIII 因子促凝活性沉淀抗体
Br J Haematol. 1982 Jan;50(1):135-46. doi: 10.1111/j.1365-2141.1982.tb01898.x.
9
Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.人血浆中凝血因子 VIII 凝血蛋白的两种不同形式。凝血酶切割作用、凝血活性差异以及与血管性血友病因子的关联
J Clin Invest. 1984 Feb;73(2):307-16. doi: 10.1172/JCI111215.
10
Measurement of antihaemophilic factor A antigen (VII:CAg) with a solid phase immunoradiometric method based on homologous non-haemophilic antibodies.采用基于同源非血友病性抗体的固相免疫放射分析法测定抗血友病因子A抗原(VII:CAg)
Scand J Haematol. 1979 Jul;23(1):17-24. doi: 10.1111/j.1600-0609.1979.tb02847.x.

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Localization of human factor FVIII inhibitor epitopes to two polypeptide fragments.
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Proc Natl Acad Sci U S A. 1985 Nov;82(22):7728-32. doi: 10.1073/pnas.82.22.7728.