骨髓增殖性肿瘤（MPN）患者和视网膜玻璃膜疣表现出补体系统失调的迹象以及高度的慢性低度炎症。
Patients with MPNs and retinal drusen show signs of complement system dysregulation and a high degree of chronic low-grade inflammation.
作者信息
Liisborg Charlotte, Skov Vibe, Kjær Lasse, Hasselbalch Hans Carl, Sørensen Torben Lykke
机构信息
Department of Ophthalmology, Zealand University Hospital, Vestermarksvej 23, Roskilde DK-4000, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
出版信息
EClinicalMedicine. 2021 Dec 25;43:101248. doi: 10.1016/j.eclinm.2021.101248. eCollection 2022 Jan.
BACKGROUND
The hematopoietic stem cell disorders, myeloproliferative neoplasms (MPNs), are characterised by chronic low-grade inflammation (CLI). Recently, we showed that patients with MPNs have an increased prevalence of drusen and age-related macular degeneration (AMD), and drusen prevalence seemed associated with higher CLI. Studying MPNs may reveal more about drusen pathophysiology. This study investigated CLI further by measuring cytokine levels and complement system markers, comparing these between patients with MPNs and AMD.
METHODS
This cross-sectional study, between July 2018 and November 2020 conducted at Zealand University Hospital (ZUH) - Roskilde, Denmark, included 29 patients with neovascular AMD (nAMD), 28 with intermediate-stage AMD (iAMD), 62 with MPNs (35 with drusen - MPNd and 27 with healthy retinas - MPNn). With flow cytometry, we measured complement-regulatory-proteins (Cregs). With immunoassays, we investigated cytokine levels combined into a summary-inflammation-score (SIS).
FINDINGS
The MPNd and nAMD groups had similar SIS, significantly higher than the MPNn and iAMD groups. Additionally, we found SIS to increase over the MPN biological continuum from early cancer stage, essential thrombocytaemia (ET), over polycythaemia vera (PV) to the late-stage primary myelofibrosis (PMF). MPNs showed signs of complement dysregulation, with Cregs expression lower in PV than ET and PMF and even lower in PV patients with drusen.
INTERPRETATION
This study suggests that MPNd have a higher CLI than MPNn and may indicate systemic CLI to play a greater part in, and even initiate drusen formation. We suggest using MPNs as a "Human Inflammation Model" of drusen development. The CLI in MPNs elicits drusen formation, triggering more CLI creating a vicious cycle, increasing the risk of developing AMD.
FUNDING
Fight for Sight, Denmark, and Region Zealand's research promotion fund.
背景
造血干细胞疾病，即骨髓增殖性肿瘤（MPN），其特征为慢性低度炎症（CLI）。最近，我们发现MPN患者玻璃膜疣和年龄相关性黄斑变性（AMD）的患病率增加，且玻璃膜疣患病率似乎与较高的CLI相关。研究MPN可能会揭示更多关于玻璃膜疣病理生理学的信息。本研究通过测量细胞因子水平和补体系统标志物，进一步研究CLI，并在MPN患者和AMD患者之间进行比较。
方法
这项横断面研究于2018年7月至2020年11月在丹麦罗斯基勒的西兰大学医院（ZUH）进行，纳入了29例新生血管性AMD（nAMD）患者、28例中期AMD（iAMD）患者、62例MPN患者（35例有玻璃膜疣的MPN - MPNd和27例视网膜健康的MPN - MPNn）。我们用流式细胞术测量补体调节蛋白（Cregs）。通过免疫测定，我们研究了细胞因子水平，并将其合并为一个综合炎症评分（SIS）。
结果
MPNd组和nAMD组的SIS相似，显著高于MPNn组和iAMD组。此外，我们发现SIS在MPN的生物学连续过程中从早期癌症阶段、原发性血小板增多症（ET）、真性红细胞增多症（PV）到晚期原发性骨髓纤维化（PMF）呈上升趋势。MPN显示出补体失调的迹象，PV患者的Cregs表达低于ET和PMF患者，有玻璃膜疣的PV患者的Cregs表达更低。
解读
本研究表明，MPNd的CLI高于MPNn，可能表明全身性CLI在玻璃膜疣形成中起更大作用，甚至引发玻璃膜疣形成。我们建议将MPN用作玻璃膜疣发展的“人类炎症模型”。MPN中的CLI引发玻璃膜疣形成，触发更多CLI，形成恶性循环，增加患AMD的风险。
资助
丹麦视力抗争组织和西兰地区研究促进基金。
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