Complement Activation Levels Are Related to Disease Stage in AMD
Complement Activation Levels Are Related to Disease Stage in AMD
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DOI：
10.1167/iovs.61.3.18
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发表时间：
2020-03-01
影响因子：
4.4
通讯作者：
Klevering, B. Jeroen
中科院分区：
文献类型：
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作者：
Heesterbeek, Thomas J.;Lechanteur, Yara T. E.;Klevering, B. Jeroen
目的.目的研究AMD患者不同疾病阶段的补体激活水平及补体基因多态性对其的影响。我们纳入了来自欧洲遗传数据库的797名AMD患者和945名对照。将患者分为五个AMD阶段：早期AMD、中期AMD、中央地图状萎缩、活动性脉络膜新生血管或非活动性脉络膜新生血管。使用一般线性模型评估了AMD分期之间的补体激活差异（由全身C3 d/C3比率定义）。此外，我们评估了18个遗传性AMD多态性对补体基因的影响及其对补体激活的作用。通过补体相关单倍型分层评价各阶段之间补体激活的差异。AMD疾病阶段之间的补体激活水平显著不同。与对照组相比，中度AMD患者C3 d/C3比值显著升高（P < 0.001），中央地图样萎缩患者C3 d/C3比值显著升高（P = 0.001）。CFH中的两个多态性（rs 10922109和rs 570618）和CFB中的一个多态性（rs 116503776）与补体激活显著相关。AMD疾病分期和补体激活之间的关联在具有与最高补体激活相关的单倍型的患者中更为明显。一般来说，连续的AMD疾病阶段显示补体激活水平增加，特别是在补体基因有遗传负担的个体中。这些发现有助于讨论AMD的发病机制与补体激活的关系，并可能建议完善患者的选择和补体抑制剂治疗的最佳窗口。需要前瞻性研究来证实这些结果。
PURPOSE. To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes.METHODS. We included 797 patients with AMD and 945 controls from the European Genetic Database. Patients were grouped into five AMD stages: early AMD, intermediate AMD, central geographic atrophy, active choroidal neovascularization or inactive choroidal neovascularization. Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. Differences in complement activation between stages were evaluated stratifying by complement associated haplotypes.RESULTS. Complement activation levels differed significantly between AMD disease stages. As compared with controls, the C3d/C3 ratio was higher in patients with intermediate AMD (P < 0.001) and central geographic atrophy (P = 0.001). Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. The association between AMD disease stage and complement activation was more pronounced in patients with haplotypes associated with the highest complement activation.CONCLUSIONS. In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. Prospective studies are needed to confirm these results.