背景:造血干细胞疾病,骨髓增殖性肿瘤(MPNs),以慢性低度炎症(CLI)为特征。最近,我们发现MPNs患者玻璃疣和年龄相关性黄斑变性(AMD)的患病率增加,玻璃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疣的病理生理学。这项研究通过测量细胞因子水平和补体系统标志物进一步调查了CLI,MPNs和AMD患者之间的比较。
方法:这项横断面研究,2018年7月至2020年11月在新西兰大学医院(ZUH)-Roskilde进行,丹麦,包括29例新生血管性AMD(nAMD)患者,28与中级AMD(iAMD),62患有MPNs(35患有玻璃疣-MPNd,27患有健康视网膜-MPNn)。用流式细胞仪,我们测量了补体调节蛋白(Cregs)。用免疫测定法,我们调查了细胞因子水平与炎症综合评分(SIS)的关系.
结果:MPNd和nAMD组的SIS相似,显著高于MPNn和iAMD组。此外,我们发现SIS从早期癌症阶段开始增加超过MPN生物学连续体,原发性血小板血症(ET),超过真性红细胞增多症(PV)至晚期原发性骨髓纤维化(PMF)。MPN显示补体失调的迹象,Cregs在PV中的表达低于ET和PMF,在患有玻璃疣的PV患者中甚至更低。
结论:这项研究表明,MPNd比MPNn具有更高的CLI,可能表明系统性CLI在,甚至开始形成玻璃疣。我们建议使用MPN作为玻璃疣发育的“人类炎症模型”。MPN中的CLI引发玻璃疣形成,触发更多CLI,造成恶性循环,增加患AMD的风险。
背景:为视觉而战,丹麦,和新西兰地区的研究促进基金。
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).
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Fight for Sight, Denmark, and Region Zealand\'s research promotion fund.