Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

• Published in: Kidney & blood pressure research 2020-10, Vol.45 (5), p.713-726
• Main Authors: Zhang, Ying, Liu, Yipeng, Liang, Liming, Liu, Liyan, Tang, Xueqing, Tang, Lijun, Chen, Ping, Chen, Juan, Wang, Zunsong, Cao, Wei, Chen, Qinlan, Zhao, Na, Xu, Dongmei
• Format: Article
• Language: English
• Subjects: Adult; Albumins; anti-phospholipase a2 receptor; Antibodies; Antigens; Autoantibodies; Binding; Biopsy; Blood pressure; complement; Complement activation; Deposition; Drug use; Enzyme-linked immunosorbent assay; Enzymes; Epidermal growth factor receptors; Female; Glomerulonephritis, Membranous - diagnosis; Glomerulonephritis, Membranous - pathology; Glomerulonephritis, Membranous - therapy; Humans; idiopathic membranous nephropathy; Immunofluorescence; Immunoglobulin G; Immunosuppressive Agents - therapeutic use; Kidney Glomerulus - drug effects; Kidney Glomerulus - pathology; Male; Mannose; Mannose-binding lectin; Mannose-Binding Lectin - analysis; Membranous nephropathy; Microscopy; Middle Aged; Nephropathy; Pathogenesis; Phospholipase; Phospholipase A2; Prognosis; Proteins; Proteinuria; Receptors, Phospholipase A2 - analysis; Regression models; Remission; Research Article; Thrombospondin; Treatment Outcome; Viral infections
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000508665

Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m 2 ), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.