Lectin Complement Pathway Activation is Associated with Massive Proteinuria in PLA2R-Positive Membranous Nephropathy: A Retrospective Study

Jiayi Li,1,2 Jiao Zhang,2 Xu Wang,2 Xumin Zheng,2 Hongmei Gao,2 Shimin Jiang,2 Wenge Li1,2 1Department of Nephrology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wenge Li, Department of Nephrology, China-Japan Friendship Hospital, No. 2, Yinghua Dong Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email wenge_lee2002@126.comIntroduction: Complement activation is highly involved in membranous nephropathy. Identifying the mechanism of the complement activation pathway carries crucial therapeutic implications yet remains controversial. This study explored lectin complement pathway activation in PLA2R-associated membranous nephropathy (MN).Methods: One hundred and seventy-six patients with biopsy-proven PLA2R-associated MN were enrolled in the retrospective study and divided into the remission group (24-hour urine protein < 0.75g and serum albumin > 35 g/L) and the nephrotic syndrome group. The clinical manifestation and C3, C4d, C1q, MBL, and B factor in renal biopsy tissues and C3, C4, and immunoglobulins in serum were evaluated.Results: Deposition of glomerular C3, C4d, and mannose-binding lectin (MBL) was significantly higher in the activated state than in the remission state in PLA2R-associated MN. MBL deposition was the risk factor for no remission. During follow-up, the persistent non-remission patients have significantly lower serum C3 levels.Conclusion: Activation of the lectin complement pathway in PLA2R-associated MN may contribute to proteinuria progression and disease activity.Keywords: membranous nephropathy, anti-PLA2R antibody, complement, lectin pathway