Anti-β2-glycoprotein I Antibody-mediated Inhibition of Activated Protein C Requires Binding of β2-glycoprotein I to Phospholipids

Anti-β2-glycoprotein I Antibody-mediated Inhibition of Activated Protein C Requires Binding of β2-glycoprotein I to Phospholipids
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抗 β2-糖蛋白 I 抗体介导的活化蛋白 C 抑制需要 β2-糖蛋白 I 与磷脂结合

DOI:
10.1055/s-0037-1613265
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发表时间:
2002
影响因子:
6.7
通讯作者:
T. Ortel
T. Ortel
中科院分区:
医学2区
文献类型:
--
作者:
T. Izumi;Mary L. Pound;Z. Su;G. Iverson;T. Ortel

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摘要 为了阐明抗 β2GPI 抗体对抗磷脂抗体综合征 (APS) 血栓形成的作用,使用磷脂囊泡和纯化蛋白研究了三名患者的 IgG 对活化蛋白 C (APC) 的影响。在 β2GPI 存在的情况下,总 IgG 中的两个抑制 APC 活性,而第三个 IgG 则不然。此外,一种 IgG 在没有 β2GPI 的情况下也能抑制 APC 活性。两种抑制性 IgG 制剂中的抗 β2GPI IgG 仅在存在 β2GPI 时才抑制 APC 活性。过量的 APC 部分抑制了抑制作用,过量的磷脂囊泡几乎完全抑制了抑制作用。裂解的 β2GPI 是一种非磷脂结合形式,不支持抑制活性,即使抗 β2GPI IgG 与裂解的分子结合。这项研究证实,来自 APS 患者的抗 β2GPI 抗体可抑制 APC 活性,并证明了这些抗体的抑制活性的表达需要 β2GPI 的磷脂结合。
Summary To clarify the role(s) of anti-β2GPI antibodies on thrombosis in antiphospholipid antibody syndromes (APS), the effect of IgG from three patients on activated protein C (APC) was investigated using phospholipid vesicles and purified proteins. Two of the total IgG inhibited APC activity in the presence of β2GPI, whereas the third IgG did not. In addition, one IgG inhibited APC activity without β2GPI. Anti-β2GPI IgG from the two inhibitory IgG preparations inhibited APC activity only in the presence of β2GPI. Inhibition was suppressed partially by excess APC and almost completely by excess phospholipid vesicles. Cleaved β2GPI, a non-phospholipid-binding form, did not support inhibitory activity, even though the anti-β2GPI IgG bound to the cleaved molecule. This study confirms that anti-β2GPI antibodies from APS patients inhibit APC activity, and demonstrates the requirement of phospholipid binding of β2GPI for expression of the inhibitory activity of these antibodies.
DOI: 10.1016/s0021-9258(17)42183-1
发表时间: 1994-01
期刊: The Journal of biological chemistry
影响因子: --
作者:
M. Smirnov;C. Esmon
通讯作者: M. Smirnov;C. Esmon
DOI: 10.1021/bi982538b
发表时间: 1999
期刊: Biochemistry.
影响因子: --
作者:
Smirnov,MD;Ford,DA;Esmon,CT;Esmon,NL
通讯作者: Esmon,NL
抗磷脂抗体患者血栓形成相关的危险因素。
DOI: --
发表时间: 2001
期刊: The Journal of rheumatology.
影响因子: --
作者:
Hansen,KE;Kong,DF;Moore,KD;Ortel,TL
通讯作者: Ortel,TL