Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
Division of Nephrology and Hypertension, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
Transl Vis Sci Technol. 2022 May 2;11(5):22. doi: 10.1167/tvst.11.5.22.
Age-related macular degeneration (AMD) is an acquired degenerative disease of the retina classified into early, intermediate, and advanced AMD. A key factor in the pathogenesis of AMD is the complement system. The interaction of age and sex with the complement system may affect the risk of developing AMD. The purpose of this study was to determine if there were sex-specific differences in levels of complement factors among patients with the intermediate phenotype of AMD (iAMD) and explore the correlation between age and complement proteins.
We studied complement factors in patients with iAMD and controls without AMD. Nonparametric, rank-based linear regressions including a sex by AMD interaction were used to compare levels for each analyte. Correlations between age and complement proteins were evaluated using the Spearman rank correlation coefficient.
We found significantly higher levels of factor B and factor I in females compared with males with iAMD, whereas no differences were seen in complement levels in male and female controls. The ratios of Ba/factor B, C3a/C3, C4b/C4, and C5a/C5 were not different in males and females with iAMD.
We demonstrate disparities in a subset of systemic complement factors between females and males with iAMD, but apparent complement turnover as measured by ratios of activation fragments to intact molecules was not different between these groups. The results suggest that complement system levels, including complement regulator factor I, exhibits sex-related differences in patients with iAMD and highlights that stratification by sex might be helpful in the interpretation of clinical trials of anticomplement therapy.
年龄相关性黄斑变性（AMD）是一种后天获得性视网膜退行性疾病，可分为早期、中期和晚期 AMD。AMD 发病机制的一个关键因素是补体系统。年龄和性别与补体系统的相互作用可能会影响 AMD 的发病风险。本研究的目的是确定中间表型 AMD（iAMD）患者的补体因子是否存在性别特异性差异，并探讨年龄与补体蛋白之间的相关性。
我们研究了 iAMD 患者和无 AMD 对照者的补体因子。采用非参数、基于秩的线性回归，包括 AMD 与性别之间的交互作用，以比较每种分析物的水平。采用 Spearman 秩相关系数评估年龄与补体蛋白之间的相关性。
我们发现，与 iAMD 男性患者相比，女性患者的因子 B 和因子 I 水平显著升高，而 iAMD 男性和女性对照者的补体水平无差异。iAMD 男性和女性患者的 Ba/因子 B、C3a/C3、C4b/C4 和 C5a/C5 比值无差异。
我们证明了 iAMD 女性和男性之间一组系统性补体因子存在差异，但这些组之间激活片段与完整分子的比值所反映的补体转换似乎没有差异。这些结果表明，补体系统水平，包括补体调节因子 I，在 iAMD 患者中存在性别相关差异，突出了按性别分层可能有助于解释抗补体治疗的临床试验。
