Ham Ye Ji, Nicklason Eleanor, Wightman Tony, Akom Sarah, Sandhu Kieran, Harraka Philip, Colville Deb, Catran Andrew, Barit David, Langsford David, Pianta Tim, Foote Andrew, Buchanan Russell, Mack Heather, Savige Judy
The University of Melbourne Department of Medicine, Northern Health and Melbourne Health, Melbourne, Australia.
Renal Unit, Northern Health, Melbourne, Australia.
Kidney Int Rep. 2022 Feb 2;7(4):848-856. doi: 10.1016/j.ekir.2022.01.1063. eCollection 2022 Apr.
Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide association study risk alleles, glomerular deposits, reduced serum levels, and occasional reports of retinal drusen. This study examined drusen in SLE and their clinical significance.
This cross-sectional observational study compared individuals with SLE recruited from renal and rheumatology clinics with hospital controls. Participants were reviewed for clinical features and underwent imaging with a nonmydriatic retinal camera. Deidentified images were examined by 2 trained graders for drusen number and size using a grid overlay.
The cohort with SLE ( 65) comprised 55 women (85%) and 10 men (15%) with a median age of 47 years (interquartile range 35-59), where 23 (35%) were of southern European or Asian ancestry, and 32 (49%) had biopsy-proven lupus nephritis. Individuals with SLE had higher mean drusen numbers than controls (27 ± 60, 3 ± 9, respectively, = 0.001), more drusen counts ≥10 (31, 48% and 3, 5%, respectively, < 0.001), and more medium-large drusen (14, 22% and 3, 5%, respectively, < 0.001). In SLE, mean drusen counts were higher, and drusen were larger, with an estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m ( = 0.02, = 0.02, respectively) or class IV nephritis ( = 0.03, = 0.02).
Drusen composition resembles that of glomerular immune deposits. CFH controls complement activation in the extracellular matrix and risk variants are shared by drusen in macular degeneration and by SLE. CFH represents a possible treatment target for SLE especially with renal impairment.
基于与遗传性补体缺陷、全基因组关联研究风险等位基因、肾小球沉积物、血清水平降低以及偶尔关于视网膜玻璃膜疣的报道之间的关联,补体已被认为与系统性红斑狼疮(SLE)的发病机制有关。本研究检查了SLE患者的玻璃膜疣及其临床意义。
这项横断面观察性研究将从肾脏和风湿病诊所招募的SLE患者与医院对照进行了比较。对参与者进行临床特征评估,并使用免散瞳视网膜相机进行成像。两名经过培训的评分员使用网格叠加法检查去识别化的图像,以确定玻璃膜疣的数量和大小。
SLE队列(65例)包括55名女性(85%)和10名男性(15%), 中位年龄为47岁(四分位间距35 - 59岁),其中23例(35%)为南欧或亚洲血统,32例(49%)经活检证实为狼疮性肾炎。SLE患者的平均玻璃膜疣数量高于对照组(分别为27±60和3±9,P = 0.001),玻璃膜疣计数≥10的患者更多(分别为31例,48%和3例,5%,P < 0.001),中大型玻璃膜疣更多(分别为14例,22%和3例,5%,P < 0.001)。在SLE中,估计肾小球滤过率(eGFR)<90 ml/min/1.73 m²(P = 0.02,P = 0.02)或IV级肾炎(P = 0.03,P = 0.02)患者的平均玻璃膜疣计数更高,玻璃膜疣更大。
玻璃膜疣的成分与肾小球免疫沉积物相似。CFH控制细胞外基质中的补体激活,黄斑变性中的玻璃膜疣和SLE具有共同的风险变异。CFH是SLE尤其是合并肾功能损害时的一个可能治疗靶点。