Zaiema Shams ElDoha Galal ElDin, Elwafa Menna Allah Zakaria Mohammad Ali Abou, Hassan Shaymaa Gamal Arafa, El Adwey Radwa Hassan Abou El Fotoh, Ghorab Raghda Mohammed Mostafa, Galal Raghda El Sayed Abdel Monem
Department of Clinical and Chemical Pathology, Ain shams University, Faculty of medicine, Cairo, Egypt.
Department of Rheumatology-Internal Medicine, Ain shams University, Faculty of medicine, Cairo, Egypt.
Thromb J. 2024 Mar 28;22(1):32. doi: 10.1186/s12959-024-00598-4.
Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.
抗磷脂综合征（APLS）是一种系统性免疫失调疾病，其特征为反复出现并发症和妊娠丢失，且病因尚不明确。大多数研究聚焦于APLS的实验室检测和临床特征，但其确切病因仍有待深入探究。中性粒细胞胞外诱捕网形成（NETosis）是APLS病理生理学中一个新提出的理论，它可能是凝血与炎症之间的缺失环节，影响着疾病的进展和严重程度。本研究旨在探讨NETosis在血栓性APLS中的预后作用。我们的研究纳入了49例新诊断的APLS患者（包括原发性和继发性），这些患者符合关于明确APLS分类标准更新的国际共识声明中的临床和实验室标准，并根据血栓事件的发生情况分为血栓形成型和非血栓形成型。此外，还纳入了20例年龄和性别匹配的反应性受试者以及20例年龄和性别匹配的健康志愿者作为对照。采用酶联免疫吸附测定（ELISA）技术检测血清髓过氧化物酶（MPO）和组蛋白水平，以评估NETosis的形成。MPO和组蛋白水平均能够区分APLS病例与正常对照，MPO的显著临界值>2.09 ng/ml，组蛋白的显著临界值>1.45 ng/ml（AUC值分别为0.987和1.000）。这些值可作为APLS患者NETosis病理生理学的预测指标。此外，这些标志物与多个预后指标显著相关，包括血栓形成、较高的凝血酶原时间（PT）和国际标准化比值（INR）以及较低的血红蛋白（Hb）水平，而使用NETs抑制剂有望改善这些指标。总之，我们建议在APLS病程早期使用建议的临界值测量NETosis标志物MPO和组蛋白，这将有助于及时启动抗NETosis治疗并改善总体预后，尤其是对于血栓性APLS患者。
