Rolla R, Vidali M, Serino R, Pergolini P, Albano E, Bellomo G
Department of Medical Sciences, University A. Avogadro of East Piedmont and Interdepartmental Research Centre for Autoimmune Diseases, Novara, Italy.
Clin Exp Immunol. 2007 Jul;149(1):63-9. doi: 10.1111/j.1365-2249.2007.03404.x. Epub 2007 May 4.
Lupus anti-coagulants (LA) are a variety of anti-phospholipid antibodies characterized by their capacity to interfere with phospholipid-dependent coagulation assays. LA are increasingly recognized as important predictors of thrombosis. However, the antigen specificity of LA is still poorly characterized. Growing evidence indicates that oxidized phospholipids are among the targets of anti-phospholipid antibodies. This prompted us to investigate the role of IgG directed against different oxidized phospholipids in 164 subjects without clotting factor defects that were tested for the presence of LA using a LA-sensitive activate partial thromboplastin time (aPTT-FSL) and a screening/confirmation assay based on diluted Russell's viper venom test (dRVVT-PL). The response to aPTT-FSL was significantly (P < 0.0005) associated with high titres of IgG against oxidized phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, whereas positivity to dRVVT-PL was associated with the elevation of IgG against oxidized phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine (P < 0.0005) and phosphatidylinositol (P < 0.01). No difference in reactivity against oxidized cardiolipin was evident between the different groups. Positivity to the dRVVT-PL test was also associated significantly (P < 0.005) with the elevation of anti-cardiolipin and anti-beta(2)-glycoprotein-1 IgG. However, stepwise logistic regression demonstrated that IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylcholine were the only independent predictors of the response to dRVVT-PL assay, while IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylinositol were independent predictors of the response to aPTT-FSL test. In conclusion, autoantibodies against defined oxidized phospholipids are independent predictors of LA detection by aPTT-FSL or dRVVT-PL assays and might contribute to the variability often observed in the responses to the functional tests detecting LA.
狼疮抗凝物（LA）是一类抗磷脂抗体，其特点是能够干扰依赖磷脂的凝血试验。LA越来越被认为是血栓形成的重要预测指标。然而，LA的抗原特异性仍未得到充分表征。越来越多的证据表明，氧化磷脂是抗磷脂抗体的靶标之一。这促使我们在164名无凝血因子缺陷的受试者中，研究针对不同氧化磷脂的IgG的作用，这些受试者使用LA敏感的活化部分凝血活酶时间（aPTT-FSL）以及基于稀释罗素蝰蛇毒试验（dRVVT-PL）的筛查/确证试验检测LA的存在。对aPTT-FSL的反应与针对氧化磷脂酰丝氨酸、磷脂酰乙醇胺和磷脂酰肌醇的高滴度IgG显著相关（P<0.0005），而dRVVT-PL阳性与针对氧化磷脂酰丝氨酸、磷脂酰胆碱、磷脂酰乙醇胺（P<0.0005）和磷脂酰肌醇（P<0.01）的IgG升高相关。不同组之间针对氧化心磷脂的反应性没有明显差异。dRVVT-PL试验阳性也与抗心磷脂和抗β2糖蛋白1 IgG升高显著相关（P<0.005）。然而，逐步逻辑回归表明，识别氧化磷脂酰乙醇胺和氧化磷脂酰胆碱的IgG是对dRVVT-PL试验反应的唯一独立预测指标，而识别氧化磷脂酰乙醇胺和氧化磷脂酰肌醇的IgG是对aPTT-FSL试验反应的独立预测指标。总之，针对特定氧化磷脂的自身抗体是通过aPTT-FSL或dRVVT-PL试验检测LA的独立预测指标，可能导致在检测LA的功能试验反应中经常观察到的变异性。
