Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Werfen China, 10 Jiuxianqiao RD., Chaoyang District, Beijing, China.
Thromb Res. 2020 Jan;185:142-149. doi: 10.1016/j.thromres.2019.11.029. Epub 2019 Nov 28.
Anti-β2GPI-Domain 1 (β2GPI-D1) antibodies are considered to be a pathogenic subset of anti-β2GPI antibodies and have been strongly associated with thrombosis and pregnancy morbidity in patients with antiphospholipid syndrome (APS). We evaluated the clinical utility of anti-β2GPI-D1 IgG antibodies for stratifying the risk of thrombosis and/or pregnancy morbidity (PM) in a cohort of Chinese patients with APS and also assessed its correlation with the Global Anti-Phospholipid Syndrome Score (GAPSS).
Sera and plasma from 192 consecutive APS patients, 17 aPL carriers, 193 patients with other systemic autoimmune diseases, and 120 healthy controls were collected and the presence of aCL IgG/IgM, anti-β2GPI IgG/IgM and anti-β2GPI-D1 IgG antibodies were assessed by chemiluminescence assays (CIA). Detection of LAC was performed according to international guidelines with the use of screening, mixing and confirmation tests. Anti-phosphatidylserine-prothrombin (aPS/PT) IgG and IgM antibodies were detected by commercial ELISA kits.
Anti-β2GPI-D1 IgG antibodies showed high specificity (97.12%) and moderate sensitivity (64.32%) for the diagnosis of APS. Anti-β2GPI-D1 antibodies levels were significantly higher in patients with triple aPL positivity than in those with double (P < 0.001) and single positive aPL (P < 0.001) and correlated well with the GAPSS (rho = 0.60, P < 0.001). Anti-β2GPI-D1 antibodies presented with a higher prevalence and higher titers in patients with late pregnancy morbidity (≥10 weeks) and thrombotic APS compared to those with early pregnancy (<10 weeks) morbidity. Higher anti-β2GP1-D1 antibodies titers effectively distinguished APS from other autoimmune diseases.
This study suggests a predictive role of anti-β2GPI-D1 IgG antibodies as a strong risk factor for both thrombotic and obstetric APS (OAPS), especially for stratification comparing early PM with late PM and thrombosis.
抗β2糖蛋白 I 结构域 1(β2GPI-D1)抗体被认为是抗β2糖蛋白 I 抗体的致病性亚类,与抗磷脂综合征(APS)患者的血栓形成和妊娠并发症(PM)强烈相关。我们评估了抗β2GPI-D1 IgG 抗体在分层中国 APS 患者血栓形成和/或妊娠并发症(PM)风险方面的临床效用,还评估了其与全球抗磷脂综合征评分(GAPSS)的相关性。
收集了 192 例连续 APS 患者、17 例 aPL 携带者、193 例其他自身免疫性疾病患者和 120 例健康对照者的血清和血浆,并通过化学发光测定法(CIA)评估 aCL IgG/IgM、抗β2GPI IgG/IgM 和抗β2GPI-D1 IgG 抗体的存在。根据国际指南,使用筛选、混合和确认试验检测狼疮抗凝物(LAC)。使用商业 ELISA 试剂盒检测抗磷脂酰丝氨酸-凝血酶原(aPS/PT)IgG 和 IgM 抗体。
抗β2GPI-D1 IgG 抗体对 APS 的诊断具有高特异性(97.12%)和中等敏感性(64.32%)。三阳性 aPL 患者的抗β2GPI-D1 抗体水平明显高于双阳性(P<0.001)和单阳性 aPL 患者(P<0.001),并与 GAPSS 密切相关(rho=0.60,P<0.001)。与早孕期(<10 周)PM 相比,晚孕期(≥10 周)PM 和血栓性 APS 患者的抗β2GPI-D1 抗体的患病率和滴度更高。较高的抗β2GPI-D1 抗体滴度可以有效区分 APS 与其他自身免疫性疾病。
本研究表明抗β2GPI-D1 IgG 抗体作为血栓形成和产科 APS(OAPS)的强危险因素具有预测作用,特别是在分层比较早发性 PM 与晚发性 PM 和血栓形成方面。