Department of Pediatrics, Division of Pediatric Rheumatology, Allergy & Immunology, University of Minnesota, AO-10 Academic Office Building, 2414 S. 7th Street, Minneapolis, MN, USA.
Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
Pediatr Rheumatol Online J. 2022 Aug 20;20(1):70. doi: 10.1186/s12969-022-00732-4.
Non-criteria antiphospholipid antibodies (NC-aPL) are a relatively undefined subgroup of antiphospholipid antibodies (aPL). Knowledge about NC-aPL in adults is limited and even less is known in pediatric patients. Routine tests for antiphospholipid syndrome (APS)-a clinical state marked by the presence of aPL in association with vascular thrombosis-usually include lupus anticoagulant (LAC), anti-cardiolipin (aCL) and -beta-2 glycoprotein I (aβ2GPI). LAC is a functional screen for prothrombotic aPL, while the latter tests identify specific autoantibodies. Specific targets of NC-aPL include, but are not limited to, phosphatidylethanolamine, phosphatidylserine, and prothrombin.
We present single-center data from eight pediatric patients with NC-aPL identified during a three-year period. All patients had presenting features raising suspicion for APS. Most patients were female with a primary rheumatic disease. One patient had a stroke. Another patient had alveolar hemorrhage and pulmonary hypertension. Raynaud's phenomenon, rashes involving distal extremities, and headaches were common. Most patients had a positive LAC, yet their routine aPL tests were negative, prompting testing for NC-aPL.
Our findings suggest NC-aPL are associated with typical signs and symptoms of APS in pediatric patients. Pediatricians and pediatric subspecialists should consider NC-aPL when clinical suspicion is high and routine aPL tests are negative, particularly when LAC is positive. While guidelines for NC-aPL do not yet exist for children or adults, these autoantibodies have pathogenic potential. Actionable items could include evaluation for the presence of other (primary) rheumatic diseases, and consultation with hematologists and/or obstetricians regarding anticoagulation/platelet inhibition and thrombosis education. Future guidelines regarding NC-aPL will only be generated by gathering more data, ideally prospectively.
非标准抗磷脂抗体（NC-aPL）是抗磷脂抗体（aPL）的一个相对未定义的亚群。成人中关于 NC-aPL 的知识有限，在儿科患者中则知之更少。抗磷脂综合征（APS）的常规检测-一种以存在与血管血栓形成相关的 aPL 为特征的临床状态-通常包括狼疮抗凝剂（LAC）、抗心磷脂（aCL）和-β2-糖蛋白 I（aβ2GPI）。LAC 是血栓形成性 aPL 的功能筛查，而后者检测则识别特定的自身抗体。NC-aPL 的特定靶标包括但不限于磷脂酰乙醇胺、磷脂酰丝氨酸和凝血酶原。
我们呈现了在三年内从 8 名儿科患者中鉴定出的 NC-aPL 的单中心数据。所有患者均有提示 APS 的临床表现。大多数患者为女性，患有原发性风湿病。1 名患者发生中风。另一名患者发生肺泡出血和肺动脉高压。雷诺现象、累及四肢远端的皮疹和头痛很常见。大多数患者的 LAC 呈阳性，但常规 aPL 检测呈阴性，提示检测 NC-aPL。
我们的发现表明 NC-aPL 与儿科患者的典型 APS 体征和症状相关。当临床怀疑度高且常规 aPL 检测呈阴性时，儿科医生和儿科亚专科医生应考虑 NC-aPL，尤其是 LAC 呈阳性时。虽然目前尚无针对儿童或成人的 NC-aPL 指南，但这些自身抗体具有潜在的致病性。可采取的措施可能包括评估是否存在其他（原发性）风湿病，以及就抗凝/血小板抑制和血栓形成教育咨询血液科医生和/或妇产科医生。关于 NC-aPL 的未来指南只能通过收集更多数据（理想情况下是前瞻性收集）来制定。
