Ying Zhang1,2, Yipeng Liu1,2, Liming Liang1, Liyan Liu3, Xueqing Tang1,2, Lijun Tang1,2, Ping Chen1,2, Juan Chen1,2, Zunsong Wang1,2, Wei Cao1,2, Qinlan Chen1, Na Zhao1,2, Dongmei Xu4,5,6,7. 1. Department of Nephrology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. 2. Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. 3. Department of Nephrology, The Fifth People's Hospital of Jinan, Jinan, China. 4. Department of Nephrology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China, dongmeixu1964@163.com. 5. Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China, dongmeixu1964@163.com. 6. Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine, Jinan, China, dongmeixu1964@163.com. 7. Nephrology Research Institute of Shandong Province, Jinan, China, dongmeixu1964@163.com.
Abstract
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 m2), 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.
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 m2), 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.