Lynch Anne M, Mandava Naresh, Patnaik Jennifer L, Frazer-Abel Ashley A, Wagner Brandie D, Palestine Alan G, Mathias Marc T, Siringo Frank S, Cathcart Jennifer N, Holers V Michael
Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA.
Exsera BioLabs, University of Colorado School of Medicine, Aurora, CO, USA.
Eur J Ophthalmol. 2020 Sep;30(5):1061-1068. doi: 10.1177/1120672119857896. Epub 2019 Jun 17.
To examine the role of systemic activation of the complement system (assessed by levels of circulating C3a, Ba, and sC5b-9) in patients (n = 122) with advanced age-related macular degeneration, geographic atrophy, and neovascular age-related macular degeneration, compared with cataract controls (n = 27).
Plasma complement factors were measured using enzyme-linked immunosorbent assays. Statistical analysis included univariate and multivariate logistic regression (p < 0.05).
Adjusted for age, the odds ratios of C3a and sC5b-9 for any advanced age-related macular degeneration were 1.78 (95% confidence interval = 1.16-2.73, p < 0.01) and 1.20 (95% confidence interval = 1.04-1.39, p = 0.01), respectively. We found a significantly elevated adjusted odds ratio of C3a (adjusted odds ratio = 1.71, 95% confidence interval = 1.12-2.60, p = 0.01) and sC5b-9 (adjusted odds ratio = 1.22, 95% confidence interval = 1.04-1.43, p = 0.01) for neovascular age-related macular degeneration. Adjusted for age, neither C3a, sC5b-9, nor Ba were associated with geographic atrophy.
We suggest a role for elevated plasma levels of C3a and sC5b-9 in patients with neovascular age-related macular degeneration. The study's results reinforce the need for more investigation to assess the impact of therapeutic interventions targeted at the complement signaling pathways in age-related macular degeneration.
研究补体系统全身激活(通过循环C3a、Ba和sC5b-9水平评估)在122例晚期年龄相关性黄斑变性、地图样萎缩和新生血管性年龄相关性黄斑变性患者中的作用,并与27例白内障对照患者进行比较。
采用酶联免疫吸附测定法检测血浆补体因子。统计分析包括单变量和多变量逻辑回归(p<0.05)。
校正年龄后,任何晚期年龄相关性黄斑变性患者C3a和sC5b-9的比值比分别为1.78(95%置信区间=1.16-2.73,p<0.01)和1.20(95%置信区间=1.04-1.39,p=0.01)。我们发现新生血管性年龄相关性黄斑变性患者C3a(校正比值比=1.71,95%置信区间=1.12-2.60,p=0.01)和sC5b-9(校正比值比=1.22,95%置信区间=1.04-1.43,p=0.01)的校正比值比显著升高。校正年龄后,C3a、sC5b-9和Ba均与地图样萎缩无关。
我们认为血浆C3a和sC5b-9水平升高在新生血管性年龄相关性黄斑变性患者中起作用。该研究结果强化了进一步研究以评估针对年龄相关性黄斑变性补体信号通路的治疗干预措施影响的必要性。