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. 2019 Aug 9;20(1):313.
doi: 10.1186/s12882-019-1509-5.

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

Mu-Fan Zhang  1   2   3   4 , Jing Huang  1   2   3   4 , Yi-Miao Zhang  1   2   3   4 , Zhen Qu  1   2   3   4 , Xin Wang  1   2   3   4 , Fang Wang  1   2   3   4 , Li-Qiang Meng  1   2   3   4 , Xu-Yang Cheng  1   2   3   4 , Zhao Cui  5   6   7   8 , Gang Liu  1   2   3   4 , Ming-Hui Zhao  1   2   3   4   9
Affiliations

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

Mu-Fan Zhang et al. BMC Nephrol. .

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.

Keywords: C3a; C5a; Complement; PLA2R; Primary membranous nephropathy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Complement activation in the plasma and urine of the patients with pMN, FSGS, and MCD and healthy controls. The plasma values were corrected by eGFR and the urine values were corrected by urinary creatinine and urinary protein. All the data were log10-transformed
Fig. 2
Fig. 2
The pathways of complement activation in the plasma and urine of the patients with pMN, FSGS, and MCD and healthy controls. The plasma values were corrected by eGFR and the urine values were corrected by urinary creatinine and urinary protein. All the data were log10-transformed
Fig. 3
Fig. 3
Correlations between the levels of complement components and the clinical data of patients with pMN. The plasma values were corrected by eGFR and the urine values were corrected by urinary creatinine and protein excretion. The analyses were performed using Spearman’s rank correlation
Fig. 4
Fig. 4
The heatmap of inter-correlations among complement components in pMN patients. a: plasma levels. b: urinary levels. a and b indicated that there were strong correlation between the complement components
See this image and copyright information in PMC

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