Complement activation products in the circulation and urine of primary membranous nephropathy

Abstract Background 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...

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Main Authors: Mu-fan Zhang, Jing Huang, Yi-miao Zhang, Zhen Qu, Xin Wang, Fang Wang, Li-qiang Meng, Xu-yang Cheng, Zhao Cui, Gang Liu, Ming-hui Zhao
Format: Article
Language:English
Published: BMC 2019-08-01
Series:BMC Nephrology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12882-019-1509-5
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author Mu-fan Zhang
Jing Huang
Yi-miao Zhang
Zhen Qu
Xin Wang
Fang Wang
Li-qiang Meng
Xu-yang Cheng
Zhao Cui
Gang Liu
Ming-hui Zhao
author_facet Mu-fan Zhang
Jing Huang
Yi-miao Zhang
Zhen Qu
Xin Wang
Fang Wang
Li-qiang Meng
Xu-yang Cheng
Zhao Cui
Gang Liu
Ming-hui Zhao
author_sort Mu-fan Zhang
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj.art-d5e5ce856b6b428e8aee40d30733e7b62022-12-22T03:01:57ZengBMCBMC Nephrology1471-23692019-08-0120111310.1186/s12882-019-1509-5Complement activation products in the circulation and urine of primary membranous nephropathyMu-fan Zhang0Jing Huang1Yi-miao Zhang2Zhen Qu3Xin Wang4Fang Wang5Li-qiang Meng6Xu-yang Cheng7Zhao Cui8Gang Liu9Ming-hui Zhao10Department of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalDepartment of Medicine, Renal Division, Peking University First HospitalAbstract Background 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. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12882-019-1509-5Primary membranous nephropathyComplementC3aC5aPLA2R
spellingShingle Mu-fan Zhang
Jing Huang
Yi-miao Zhang
Zhen Qu
Xin Wang
Fang Wang
Li-qiang Meng
Xu-yang Cheng
Zhao Cui
Gang Liu
Ming-hui Zhao
Complement activation products in the circulation and urine of primary membranous nephropathy
BMC Nephrology
Primary membranous nephropathy
Complement
C3a
C5a
PLA2R
title Complement activation products in the circulation and urine of primary membranous nephropathy
title_full Complement activation products in the circulation and urine of primary membranous nephropathy
title_fullStr Complement activation products in the circulation and urine of primary membranous nephropathy
title_full_unstemmed Complement activation products in the circulation and urine of primary membranous nephropathy
title_short Complement activation products in the circulation and urine of primary membranous nephropathy
title_sort complement activation products in the circulation and urine of primary membranous nephropathy
topic Primary membranous nephropathy
Complement
C3a
C5a
PLA2R
url http://link.springer.com/article/10.1186/s12882-019-1509-5
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