From Inova Diagnostics Inc., San Diego, California, USA; Academic Department of Vascular Surgery, King's College London; Graham Hughes Lupus Research Laboratory, Lupus Research Unit, The Rayne Institute, Division of Women's Health, King's College London, St. Thomas' Hospital, London, UK; Department of Internal Medicine, University of Castilla-La Mancha, Albacete, Spain; Department of Experimental Medicine, La Sapienza University, Rome, Italy.
Navid Zohoury, Zakera Shums, and Gary L. Norman are employees of Inova Diagnostics.
J Rheumatol. 2017 Nov;44(11):1597-1602. doi: 10.3899/jrheum.170044. Epub 2017 Sep 1.
Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests ("laboratory criteria"). These "seronegative APS" (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study's objective was to describe antibody profiles of SN-APS patients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS.
We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies.
Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APS patients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies.
Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APS patients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.
大多数临床医生使用 2006 年悉尼分类标准来评估疑似抗磷脂综合征（APS）的患者。尽管该标准对 APS 具有较高的敏感性和特异性，但许多符合该综合征临床标准的患者始终为特定血清学检测阴性（“实验室标准”）。这些“血清阴性 APS”（SN-APS）患者可能在经历严重临床事件之前一直未被诊断和治疗。本研究的目的是使用非标准标志物描述 SN-APS 患者的抗体谱，分别评估这些标志物的临床效用，并将其组合使用，为疑似 APS 的患者提出纳入指南的建议。
我们将 175 例连续疑似 APS 的患者分为 2 个亚组：107 例符合悉尼 APS 分类标准的血清阳性 APS（SP-APS），68 例具有 APS 临床表现但两次均为阴性的患者，其血清学检测标准标志物阴性（SN-APS）。在研究纳入时，对所有患者的样本进行了重新检测，以评估标准和 11 种非标准标志物，包括抗磷脂酰丝氨酸/凝血酶原抗体。
使用 11 种非标准检测中的 4 种，检测到 30.9%的 SN-APS 患者。将所有 11 种非标准检测的结果相结合，25 例 SN-APS（36.8%）和 89 例 SP-APS（83.2%）患者的 1 种或多种非标准抗体检测结果为阳性。
未能诊断 APS 可能导致严重的临床后果。表现出 APS 临床特征但常规标准标志物阴性的患者应进行额外的非标准生物标志物检测。在我们的队列中，约三分之一的 SN-APS 患者对 1 种或多种非标准标志物有反应。应考虑更新当前的分类标准，纳入新的血清学标志物，以识别和分层 APS 患者，从而进行更有效的治疗和管理。
