权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Research on the standardization of the assays for anticardiolipin antibodies.

抗心磷脂抗体检测标准化研究。

基本信息

批准号：
11670431
负责人：
ICHIKAWA Kenji
金额：
$ 2.18万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670431/
关键词：
antiphospholipid syndrome anticardiolipin antibody anti-β2-GPI antibody thrombosis fetal loss SLE chimeric antibody autoimmune disease anticardiolipin antibody anti-β2-glycoprotein I antibody thrombesis Chimeric antibody 抗リン脂質抗体症候群

项目摘要

Anticardiolipin antibodies (aCL) which recognize epitope on β2-glycoprotein I (β2-GPI) is a marker of antiphospholipid syndrome (APS), and considered to be pathogenic. However, the lack of a proper international standard for measurement of aCL and anti-β2-GPI antibodies make it difficult to compare data from different laboratories. To standardize the assay for aCLs and anti-β2-GPI antibodies is important for clinical investigation of APS and for studies on pathophysiology of antiphospholipid syndrome.We already established EY2C9, IgM monoclonal aCL derived from an APS patient, which is suitable for a standard of IgM aCL and anti-β2-GPI assays, but did not have a human IgG monoclonal aCL.Therefore, plasmids containing variable region genes of WBCAL-1, which is a monoclonal aCL derived from an APS prone mouse, and human γ1 and κ constant region genes were made. The constructs were transfected to P3U1, a mouse myeloma cell line and tarnsfected cells which secreted HCAL, a chimeric antibody, were cloned.EY2C9 and HCALA had the similar characteristics as aCL detected in sera from APS patients and high avidity to 2-GPI.Those antibodies worked well in most of the representative laboratories studying aCLs and ant-β2-glycoprotein I antibodies in the world, and are approved as standards for assay for aCLs by NIH and FDA.Cell line which secreting HCALA, a chimeric antibody consisting of variable regions of WBCAL-1 and human α1 and κ constant regions, was established in the same methods. HCALA recognized β2-GPI bound to CL or to oxygenated polystyrene surface. This binding profile is similar to that of aCL in sera from APS patients. The avidity of HCALA was high enough for a standard of aCL and anti-β2-GPI antibody assays.

抗心磷脂抗体（aCL）识别β2-糖蛋白I（β2-GPI）上的表位，是抗磷脂综合征（APS）的标志物，被认为是致病性的。然而，由于缺乏适当的国际标准来测量aCL和抗β2-GPI抗体，因此难以比较来自不同实验室的数据。本实验室已建立了一株来源于APS患者的EY 2C 9、IgM单克隆aCL，可作为检测抗β2-GPI抗体和抗β 2-GPI抗体的标准，但尚未建立人IgG单克隆aCL，因此，本实验室构建了含有WBCAL-1可变区基因的质粒，其是来源于APS易感小鼠的单克隆aCL，以及人γ1和κ恒定区基因。EY 2C 9和HCALA具有与APS患者血清中aCL相似的特性，对2-GPI具有较高的亲和力，在国际上大多数aCL和抗β2-gp I抗体的代表性实验室中均获得了良好的效果，用同样的方法建立了分泌由WBCAL-1可变区与人α1和κ恒定区组成的嵌合抗体HCALA的细胞系。HCALA识别与CL或氧化聚苯乙烯表面结合的β2-GPI。这种结合特征与APS患者血清中的aCL相似。HCALA的亲合力足以用于aCL和抗β2-GPI抗体测定的标准。