Miao Di, Ma Tian-Tian, Chen Min, Zhao Ming-Hui
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University.
Key Laboratory of Renal Disease, Ministry of Health of China.
Rheumatology (Oxford). 2019 Mar 6. doi: 10.1093/rheumatology/kez044.
The biological functions of the platelets contributing to ANCA-associated vasculitis (AAV) are largely unclear. The current study aimed to investigate the potential role of platelet-derived microparticles (PMPs) in AAV.
In the current study, microparticles in AAV patients were analysed by flow cytometry, and PMPs were probed for relative levels of 640 bioactive proteins secreted from patients' platelets using antibody microarrays. These data were then correlated with clinical and pathological parameters.
PMPs were significantly increased in 69 AAV patients, predominantly MPO-ANCA positive patients in active stage compared with in remission [4406.8/μl (2135.4, 5485.0) vs 549.7/μl (350, 708.5), P < 0.0001], and 43% of microparticles in active AAV were PMPs. Compared with 15 patients in remission, highly expressed proinflammatory molecules in the microparticles from platelets in 15 AAV patients in active stage revealed that potential functions of PMPs were promotion of the effect of chemotaxis, adhesion, growth and apoptosis (all the patients for array analysis were MPO-ANCA positive). The level of PMPs had a significant association with disease activity, inflammation, and renal damage.
PMPs may serve as inflammatory propagators through their wide production of proinflammatory cytokines in AAV, potentially providing a novel therapeutic target.
血小板在抗中性粒细胞胞浆抗体相关性血管炎(AAV)中所起的生物学功能在很大程度上尚不清楚。本研究旨在探讨血小板衍生微粒(PMPs)在AAV中的潜在作用。
在本研究中,通过流式细胞术分析AAV患者的微粒,并使用抗体微阵列检测PMPs中患者血小板分泌的640种生物活性蛋白的相对水平。然后将这些数据与临床和病理参数相关联。
69例AAV患者的PMPs显著增加,与缓解期相比,主要是活动期的髓过氧化物酶抗中性粒细胞胞浆抗体(MPO-ANCA)阳性患者[4406.8/μl(2135.4,5485.0)对549.7/μl(350,708.5),P<0.0001],且活动期AAV中43%的微粒为PMPs。与15例缓解期患者相比,15例活动期AAV患者血小板微粒中高表达的促炎分子表明,PMPs的潜在功能是促进趋化、黏附、生长和凋亡作用(所有用于阵列分析的患者均为MPO-ANCA阳性)。PMPs水平与疾病活动度、炎症及肾损害显著相关。
在AAV中,PMPs可能通过大量产生促炎细胞因子而充当炎症传播者,这可能为提供一个新的治疗靶点。