Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma, Viale del Policlinico 155, Rome, Italy.
Clin Exp Immunol. 2012 Mar;167(3):429-37. doi: 10.1111/j.1365-2249.2011.04532.x.
In clinical practice it is possible to find patients with clinical signs suggestive of anti-phospholipid syndrome (APS) who are persistently negative for the routinely used anti-phospholipid antibodies (aPL). Therefore, the term proposed for these cases was seronegative APS (SN-APS). We investigated the clinical usefulness of thin-layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN-APS. Sera from 36 patients with SN-APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti-hepatitis C virus (HCV)-positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti-β(2) -glycoprotein-I, anti-annexin II, anti-annexin V and anti-prothrombin antibodies were tested by enzyme-linked immunosorbent assays (ELISA). Eahy926, a human-derived endothelial cell line, was incubated with immunoglobulin (Ig)G fraction from SN-APS patients and analysis of phospho-interleukin (IL)-1 receptor-associated kinase (IRAK) and phospho-nuclear factor (NF)-κB was performed by Western blot, vascular cell adhesion molecule 1 (VCAM-1) expression by cytofluorimetric analysis and supernatants tissue factor (TF) levels by ELISA. TLC immunostaining showed aPL in 58·3% of SN-APS patients: anti-cardiolipin in 47·2%, anti-lyso(bis)phosphatidic acid in 41·7% and anti-phosphatidylethanolamine in 30·5%. Six of 36 patients showed anti-annexin II. Incubation of Eahy926 cells with IgG from SN-APS induced IRAK phosphorylation, NF-κB activation, VCAM-1 surface expression and TF cell release. TLC immunostaining could identify the presence of aPL in patients with SN-APS. Moreover, the results suggest the proinflammatory and procoagulant effects in vitro of these antibodies.
在临床实践中,有可能发现具有抗磷脂综合征(APS)临床体征的患者,但常规使用的抗磷脂抗体(aPL)持续为阴性。因此,这些病例被称为血清阴性抗磷脂综合征(SN-APS)。我们研究了薄层色谱(TLC)免疫染色在检测具有 SN-APS 临床特征的患者血清 aPL 中的临床应用。用 TLC 免疫染色法检测 36 例 SN-APS 患者、19 例 APS 患者、18 例系统性红斑狼疮(SLE)患者、20 例丙型肝炎病毒(HCV)阳性患者和 32 例健康对照者的 aPL。用酶联免疫吸附试验(ELISA)检测抗β(2)-糖蛋白-I、抗心磷脂、抗膜联蛋白 II、抗膜联蛋白 V 和抗凝血酶原抗体。用人内皮细胞系 Eahy926 孵育 SN-APS 患者的 IgG 片段,通过 Western blot 分析磷酸化白细胞介素(IL)-1 受体相关激酶(IRAK)和磷酸化核因子(NF)-κB,通过细胞流式分析测定血管细胞黏附分子 1(VCAM-1)的表达,通过 ELISA 测定上清液组织因子(TF)水平。TLC 免疫染色显示 58·3%的 SN-APS 患者存在 aPL:抗心磷脂 47·2%、抗溶血磷脂酸 41·7%和抗磷脂酰乙醇胺 30·5%。36 例患者中有 6 例显示抗膜联蛋白 II。用 SN-APS 患者的 IgG 孵育 Eahy926 细胞可诱导 IRAK 磷酸化、NF-κB 激活、VCAM-1 表面表达和 TF 细胞释放。TLC 免疫染色可识别 SN-APS 患者存在 aPL。此外,这些结果提示这些抗体具有体外促炎和促凝作用。