Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
PLoS One. 2021 Jun 25;16(6):e0253716. doi: 10.1371/journal.pone.0253716. eCollection 2021.
Preclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic complement activation has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity.
Systemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy).
The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3-15%). Elevated C3d/C3 ratios (>8.1) were found in three patients who all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p = 0.001, independent samples t-test) and BMI (correlation coefficient 0.463, p<0.001, Spearman's Correlation).
Systemic complement levels were not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients.
临床前研究为补体系统作为导致视网膜色素上皮（RPE）丧失的斯塔加特病（STGD1）和年龄相关性黄斑变性（AMD）的潜在共同途径提供了证据。然而，尚未在 STGD1 患者中评估系统性补体激活。我们进行了一项横断面病例对照研究，以评估 STGD1 患者的系统性补体激活及其与疾病严重程度的关系。
比较 80 例 STGD1 患者和 80 例年龄和性别匹配的对照者的补体成分 C3 及其降解产物 C3d 的系统浓度。C3d/C3 比值用作系统补体激活的参数。在 STGD1 队列中，我们还检查了 C3d/C3 比值与人口统计学和行为因素（年龄、性别、吸烟和 BMI）以及疾病严重程度测量值（发病年龄、视力和萎缩面积）之间的关系。
患者（平均 C3d/C3 比值 3.5±1.4）和对照组（平均 C3d/C3 比值 3.6±1.0）之间的 C3d/C3 比值无显着差异，平均差异-0.156（p = 0.804，独立样本 t 检验）。总体效应大小为 8%（95%置信区间，3-15%）。在 3 名患者中发现 C3d/C3 比值升高（>8.1），他们在采血时均伴有合并炎症性疾病。在患者队列中，C3 水平与性别相关（平均差异-134，p = 0.001，独立样本 t 检验）和 BMI（相关系数 0.463，p<0.001，Spearman 相关）。
与年龄和性别匹配的对照组相比，STGD1 患者的系统性补体水平没有升高，并且与 STGD1 严重程度无关。考虑到补体系统对 RPE 丧失的系统性贡献仍然没有得到证明，我们假设 STGD1 中的补体激活更可能是局部过程。鉴于即将进行的补体靶向治疗，需要进一步研究测量 STGD1 患者眼中的补体水平。
