University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital, and Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy.
Exagen Inc., Vista, CA, United States.
Front Immunol. 2022 Aug 10;13:949919. doi: 10.3389/fimmu.2022.949919. eCollection 2022.
Classification criteria for antiphospholipid syndrome (APS) require that antiphospholipid antibody (aPL) positivity is confirmed after at least 12 weeks. We tested the hypothesis that aPL at high titers remain positive while low titers fluctuate over time. As both platelet-bound C4d (PC4d) and aPL are associated with thrombosis in systemic lupus erythematosus (SLE), we also evaluated whether PC4d can aid in APS diagnosis.
Data from serum or plasma sent to Exagen's laboratory for routine aPL testing were analyzed. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein-1 antibodies (aB2GP1) were measured by chemiluminescence or ELiA fluorescence enzyme immunoassay; anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) by ELISA; PC4d by flow cytometry. Statistical analysis included descriptive statistics, logistic regression, and Pearson correlation.
More than 80% of positive samples with aCL and aB2GP1 at high titers - but not low titers - were positive at a retest. Non-criteria aPL (aPS/PT) followed a similar trend. aCL and aB2GP1 measured with two different technologies were highly correlated. PC4d and IgG of the three aPL were at best moderately correlated even when only positive aPL samples were analyzed (coefficient: 0.1917 to 0.2649).
High titers aPL are often persistently positive, allowing an earlier diagnosis and risk assessment at the time of the initial screening. Conversely, a retest may be necessary for low titers. The high correlation between two methodologies suggests that these findings are independent of assay platform. The low to moderate correlation between PC4d and aPL might suggest a possible additive value to evaluate association with thrombosis in autoimmune diseases.
抗磷脂综合征（APS）的分类标准要求抗磷脂抗体（aPL）阳性在至少 12 周后得到确认。我们检验了以下假说，即高滴度的 aPL 持续阳性，而低滴度的 aPL 随时间波动。由于血小板结合的补体 C4d（PC4d）和 aPL 均与系统性红斑狼疮（SLE）中的血栓形成有关，我们还评估了 PC4d 是否有助于 APS 的诊断。
分析了送往 Exagen 实验室进行常规 aPL 检测的血清或血浆数据。用化学发光或 ELiA 荧光酶免疫分析法检测抗心磷脂（aCL）和抗β2 糖蛋白 1 抗体（aB2GP1）；用酶联免疫吸附试验检测抗磷脂酰丝氨酸/凝血酶原复合物抗体（aPS/PT）；用流式细胞术检测 PC4d。统计分析包括描述性统计、逻辑回归和 Pearson 相关性分析。
高滴度 aCL 和 aB2GP1 的阳性样本中，超过 80%的样本在复测时仍为阳性——但低滴度的样本则不然。非标准 aPL（aPS/PT）也呈现出类似的趋势。两种不同技术检测的 aCL 和 aB2GP1 高度相关。即使仅分析阳性 aPL 样本，PC4d 和三种 aPL 的 IgG 之间的相关性也仅为中等程度（系数：0.1917 至 0.2649）。
高滴度 aPL 通常持续阳性，这使得在初次筛查时可以更早地进行诊断和风险评估。相反，对于低滴度的 aPL，则可能需要复测。两种方法学之间的高相关性表明，这些发现独立于检测平台。PC4d 与 aPL 之间的低到中度相关性可能表明其对评估自身免疫性疾病中的血栓形成有一定的附加价值。
