从抗磷脂综合征的（新西兰白兔×BXSB）F1小鼠模型中建立的单克隆抗心磷脂自身抗体与氧化型低密度脂蛋白发生交叉反应。

Monoclonal anticardiolipin autoantibodies established from the (New Zealand white x BXSB)F1 mouse model of antiphospholipid syndrome cross-react with oxidized low-density lipoprotein.

作者信息

Mizutani H, Kurata Y, Kosugi S, Shiraga M, Kashiwagi H, Tomiyama Y, Kanakura Y, Good R A, Matsuzawa Y

机构信息

Second Department of Internal Medicine, Osaka University Medical School, Japan.

出版信息

Arthritis Rheum. 1995 Oct;38(10):1382-8. doi: 10.1002/art.1780381005.

DOI:10.1002/art.1780381005

PMID:7575688

Abstract

OBJECTIVE

Autoimmunity-prone (New Zealand white x BXSB)F1 ([NZW x BXSB]F1) mice have been shown to be useful as a model of antiphospholipid syndrome with myocardial infarction. The aim of this study was to examine the cross-reactivity of anticardiolipin antibody (aCL) derived from (NZW x BXSB)F1 mice with oxidized low-density lipoprotein (ox-LDL), which is closely associated with atherosclerosis.

METHODS

Six monoclonal antibodies (MAb) against CL were established from (NZW x BXSB)F1 mice, and reactivity of aCL with ox-LDL was examined by micro-enzyme-linked immunosorbent assay.

RESULTS

Higher titers of anti-ox-LDL autoantibodies were found in adult (NZW x BXSB)F1 mice compared with other autoimmunity-prone mouse strains (P < 0.01) or a control strain (P < 0.005). There was a significant positive correlation between titers of aCL and those of anti-ox-LDL in (NZW x BXSB)F1 mice (r = 0.79, P < 0.001). Of the 6 MAb against CL, 2 clones that showed beta 2-glycoprotein 1-dependent reactivity also cross-reacted with ox-LDL. Binding of monoclonal aCL to solid-phase cardiolipin was inhibited by ox-LDL, but not by native LDL.

CONCLUSION

We confirmed that aCL derived from (NZW x BXSB)F1 mice can cross-react with ox-LDL. This result suggests that aCL, which is closely associated with lupus-associated thrombosis, may also play an important role in atherosclerotic complications in patients with systemic lupus erythematosus.

摘要

目的

自身免疫易感的（新西兰白兔×BXSB）F1（[NZW×BXSB]F1）小鼠已被证明是心肌梗死抗磷脂综合征的有用模型。本研究的目的是检测源自（NZW×BXSB）F1小鼠的抗心磷脂抗体（aCL）与氧化低密度脂蛋白（ox-LDL）的交叉反应性，氧化低密度脂蛋白与动脉粥样硬化密切相关。

方法

从（NZW×BXSB）F1小鼠中建立了6种抗心磷脂单克隆抗体（MAb），并通过微酶联免疫吸附测定法检测aCL与ox-LDL的反应性。

结果

与其他自身免疫易感小鼠品系（P<0.01）或对照品系（P<0.005）相比，成年（NZW×BXSB）F1小鼠中抗ox-LDL自身抗体的滴度更高。在（NZW×BXSB）F1小鼠中，aCL滴度与抗ox-LDL滴度之间存在显著正相关（r=0.79，P<0.001）。在6种抗心磷脂MAb中，2个显示β2-糖蛋白1依赖性反应性的克隆也与ox-LDL发生交叉反应。单克隆aCL与固相心磷脂的结合受到ox-LDL的抑制，但不受天然LDL的抑制。