Department of Medicine, Renal Division, Peking University First Hospital, Beijing, 100034, China.
Institute of Nephrology, Peking University, Beijing, 100034, China.
BMC Nephrol. 2019 Aug 9;20(1):313. doi: 10.1186/s12882-019-1509-5.
Complement activation plays a substantial role in the pathogenesis of primary membranous nephropathy (pMN). C5b-9, C3c, MBL, and factor B have been documented in the subepithelial immune deposits. However, the changing of complement activation products in circulation and urine is not clear.
We measured the circulating and urinary levels of C1q, MBL, C4d, Bb, properdin, C3a, C5a, and sC5b-9, in 134 patients with biopsy-proven pMN, by enzyme-linked immunosorbent assay. All the plasma values were corrected by eGFR and all the urinary values were corrected by urinary creatinine and urinary protein excretion. Anti-PLA2R antibodies were measured in all patients.
The plasma complement activation products were elevated both in the patients with and without anti-PLA2R antibodies. C3a levels were remarkably increased in the circulation and urine, much higher than the elevated levels of C5a. C5b-9 was in normal range in plasma, but significantly higher in urine. The urinary C5a had a positive correlation with anti-PLA2R antibody levels and urinary protein. The plasma level of C4d was elevated, but C1q and MBL were comparable to healthy controls. Positive correlations were observed between plasma C4d/MBL and urinary protein, only in the patients with positive anti-PLA2R antibodies but not in those without. The plasma level of Bb was elevated and had positive correlation with urinary protein only in the patients without anti-PLA2R antibodies.
Complement activation products were remarkable increased in pMN and may serve as sensitive biomarkers of disease activity. The complement may be activated through lectin pathway with the existence of anti-PLA2R antibodies, while through alternative pathway in the absence of antibody.
补体激活在原发性膜性肾病（pMN）的发病机制中起重要作用。已经在基板下免疫沉积物中记录了 C5b-9、C3c、MBL 和因子 B。然而，循环和尿液中补体激活产物的变化尚不清楚。
我们通过酶联免疫吸附试验测量了 134 例经活检证实的 pMN 患者的循环和尿液中的 C1q、MBL、C4d、Bb、properdin、C3a、C5a 和 sC5b-9 水平。所有血浆值均通过 eGFR 校正，所有尿液值均通过尿肌酐和尿蛋白排泄校正。所有患者均测量了抗-PLA2R 抗体。
有和没有抗-PLA2R 抗体的患者的血浆补体激活产物均升高。C3a 水平在循环和尿液中显着升高，远高于升高的 C5a 水平。C5b-9 在血浆中处于正常范围，但在尿液中显着升高。尿 C5a 与抗-PLA2R 抗体水平和尿蛋白呈正相关。血浆 C4d 水平升高，但 C1q 和 MBL 与健康对照组相当。仅在抗-PLA2R 抗体阳性的患者中观察到血浆 C4d/MBL 与尿蛋白之间存在正相关，而在抗-PLA2R 抗体阴性的患者中则没有。Bb 的血浆水平升高，仅在无抗-PLA2R 抗体的患者中与尿蛋白呈正相关。
pMN 中补体激活产物显着增加，可作为疾病活动的敏感生物标志物。在存在抗-PLA2R 抗体的情况下，补体可能通过凝集素途径激活，而在没有抗体的情况下通过替代途径激活。
