Surmiak Marcin, Hubalewska-Mazgaj Magdalena, Wawrzycka-Adamczyk Katarzyna, Szczeklik Wojciech, Musiał Jacek, Brzozowski Tomasz, Sanak Marek
Department of Internal Medicine, and Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
Clin Exp Rheumatol. 2016 May-Jun;34(3 Suppl 97):S98-104. Epub 2016 May 17.
Granulomatosis with polyangiitis (GPA) is an autoimmune disease with still unknown etiology. Recent studies indicate that neutrophils extra-cellular traps participate in the pathophysiology of GPA. This study investigates the levels of circulating NET formation markers and neutrophil-platelet interaction in patients with GPA.
We enrolled 40 GPA patients (20 in the active stage of the disease and 20 in remission). Twenty sex- and age-matched healthy subjects served as a control group. Serum/plasma levels of serine proteases, and histone-, myeloperoxidase-, proteinase-3 DNA complexes and sP-selectin were measured using ELISA or Luminex assays. Circulating platelet-neutrophil aggregates and neutrophils activation markers expression was measured by flow cytometry.
Patients in active stage of GPA had higher circulating levels of serine proteases, DNA-histone and myeloperoxidase -DNA complexes. In addition, platelet-neutrophil aggregates and sP-selectin were also elevated in this group. Platelet-neutrophil aggregates and myeloperoxidase -DNA complexes correlated positively with the disease activity score (BVAS).
NETs production and activation of platelets in GPA is supported by elevated myeloperoxidase-DNA complexes and platelet-neutrophil aggregates correlating positively with the disease activity score. This mechanism justifies laboratory measurements of myeloperoxidase-DNA complexes and plasma sP-selectin as biomarkers for studying GPA activity.
肉芽肿性多血管炎（GPA）是一种病因仍不明的自身免疫性疾病。近期研究表明，中性粒细胞胞外陷阱参与了GPA的病理生理学过程。本研究旨在调查GPA患者循环中NET形成标志物的水平以及中性粒细胞与血小板的相互作用。
我们纳入了40例GPA患者（疾病活动期20例，缓解期20例）。20名年龄和性别匹配的健康受试者作为对照组。使用ELISA或Luminex检测法测量血清/血浆中丝氨酸蛋白酶、组蛋白、髓过氧化物酶、蛋白酶-3 DNA复合物和sP-选择素的水平。通过流式细胞术检测循环中的血小板-中性粒细胞聚集体以及中性粒细胞活化标志物的表达。
GPA活动期患者循环中丝氨酸蛋白酶、DNA-组蛋白和髓过氧化物酶-DNA复合物的水平较高。此外，该组患者的血小板-中性粒细胞聚集体和sP-选择素也升高。血小板-中性粒细胞聚集体和髓过氧化物酶-DNA复合物与疾病活动评分（BVAS）呈正相关。
GPA中NETs的产生和血小板的活化得到了髓过氧化物酶-DNA复合物升高以及血小板-中性粒细胞聚集体与疾病活动评分呈正相关的支持。这一机制证明了将髓过氧化物酶-DNA复合物和血浆sP-选择素作为研究GPA活动的生物标志物进行实验室检测的合理性。
