Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Rheumatol. 2013 Mar;40(3):282-6. doi: 10.3899/jrheum.120084. Epub 2013 Feb 1.
Currently, 3 antiphospholipid assays are widely used clinically [lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-ß2-glycoprotein I (anti-ß2-GPI)]. LAC is the most specific assay, conferring the highest risk of thrombosis and pregnancy loss, but it cannot be validly performed in an anticoagulated patient. We investigated the usefulness of antiphosphatidylserine/prothrombin (anti-PS/PT) and its association with thrombosis. Anti-PS/PT is strongly associated with the presence of LAC. We also studied the association of IgA antiphospholipid isotypes and specific domains of ß2-GPI with thrombosis in systemic lupus erythematosus (SLE).
Stored samples from patients with SLE, with and without past thrombosis, were assayed for antibodies to the whole ß2-GPI protein (IgG/IgM/IgA), to ß2-GPI domain 1 (IgG), to ß2-GPI domain 4/5 (IgA), aCL (IgG/IgM/IgA), and anti-PS/PT (IgG, IgM, and IgG/M). LAC was detected using the dilute Russell's viper venom time (dRVVT) with confirmatory testing.
Anti-PS/PT IgG and IgG/M and anti-ß2-GPI IgG, IgM, and IgA were highly associated with a history of LAC by dRVVT (p < 0.0001). For all thrombosis, of the traditional ELISA assays, anti-ß2-GPI IgA, IgG, and aCL IgA were most associated. Anti-PS/PT IgG and IgG/M had a similar magnitude of association to the traditional ELISA. For venous thrombosis, of the traditional ELISA, anti-ß2-GPI (IgG and IgA), anti-PS/PT (IgG and IgG/M), and aCL IgA were associated. Again, anti-PS/PT (IgG and IgG/M) had the same magnitude of association as the traditional ELISA. For stroke, significant association was seen with anti-ß2-GPI IgA D4/5.
In anticoagulated patients, where LAC testing is not valid, anti-PS/PT, either IgG or IgG/IgM, might serve as useful alternative tests to predict a higher risk of thrombosis. Anti-PS/PT antibodies were associated with all thrombosis and with venous thrombosis. IgA isotypes in secondary antiphospholipid syndrome are associated with thrombosis. Anti-ß2-glycoprotein domain 1 was not shown to be associated with thrombosis in SLE.
目前临床上广泛使用 3 种抗磷脂抗体检测方法[狼疮抗凝物（LAC）、抗心磷脂（aCL）和抗β2-糖蛋白 I（抗β2-GPI）]。LAC 是最特异的检测方法，可导致血栓形成和妊娠丢失的风险最高，但在抗凝患者中无法有效进行。我们研究了抗磷脂酰丝氨酸/凝血酶原（抗 PS/PT）的有用性及其与血栓形成的关系。抗 PS/PT 与 LAC 的存在强烈相关。我们还研究了 IgA 型抗磷脂抗体同种型和β2-GPI 特异性结构域与系统性红斑狼疮（SLE）血栓形成的关系。
检测了伴有和不伴有既往血栓形成的 SLE 患者的储存样本，以检测针对整个β2-GPI 蛋白（IgG/IgM/IgA）、β2-GPI 结构域 1（IgG）、β2-GPI 结构域 4/5（IgA）、aCL（IgG/IgM/IgA）和抗 PS/PT（IgG、IgM 和 IgG/M）的抗体。使用稀释的 Russell's 蝰蛇毒时间（dRVVT）检测 LAC，并用确认试验进行确认。
抗 PS/PT IgG 和 IgG/M 以及抗β2-GPI IgG、IgM 和 IgA 与 dRVVT 检测的 LAC 病史高度相关（p < 0.0001）。对于所有血栓形成，在传统 ELISA 检测中，抗β2-GPI IgA、IgG 和 aCL IgA 相关性最强。抗 PS/PT IgG 和 IgG/M 与传统 ELISA 具有相似的相关性。对于静脉血栓形成，在传统 ELISA 中，抗β2-GPI（IgG 和 IgA）、抗 PS/PT（IgG 和 IgG/M）和 aCL IgA 与血栓形成相关。同样，抗 PS/PT（IgG 和 IgG/M）与传统 ELISA 具有相同的相关性。对于中风，抗β2-GPI IgA D4/5 与显著相关性相关。
在抗凝患者中，LAC 检测无效时，抗 PS/PT IgG 或 IgG/M 可能是预测血栓形成风险较高的有用替代检测方法。抗 PS/PT 抗体与所有血栓形成和静脉血栓形成相关。继发性抗磷脂综合征的 IgA 同种型与血栓形成相关。β2-糖蛋白结构域 1 与 SLE 中的血栓形成无关。
