Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 22;15(6):e0234934.
doi: 10.1371/journal.pone.0234934. eCollection 2020.

Complement activation profile of patients with primary focal segmental glomerulosclerosis

Jing Huang  1   2   3   4 , Zhao Cui  1   2   3   4 , Qiu-Hua Gu  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 , Xu-Yang Cheng  1   2   3   4 , Li-Qiang Meng  1   2   3   4 , Gang Liu  1   2   3   4 , Ming-Hui Zhao  1   2   3   4   5
Affiliations

Complement activation profile of patients with primary focal segmental glomerulosclerosis

Jing Huang et al. PLoS One. .

Abstract

Background: Studies on adriamycin mice model suggest complement system is activated and together with IgM contributes to the glomerular injury of primary focal segmental glomerulosclerosis (FSGS). We recently reported primary FSGS patients with IgM and C3 deposition showed unfavorable therapeutic responses and worse renal outcomes. Here we examined the plasma and urinary complement profile of patients with primary FSGS, aiming to investigate the complement participation in FSGS pathogenesis.

Methods: Seventy patients with biopsy-proven primary FSGS were enrolled. The plasma and urinary levels of C3a, C5a, soluble C5b-9, C4d, C1q, MBL, and Bb were determined by commercial ELISA kits.

Results: The levels of C3a, C5a and C5b-9 in plasma and urine of FSGS patients were significantly higher than those in normal controls. The plasma and urinary levels of C5b-9 were positively correlated with urinary protein, renal dysfunction and interstitial fibrosis. The plasma C5a levels were positively correlated with the proportion of segmental sclerotic glomeruli. The urinary levels of Bb were elevated, positively correlated with C3a and C5b-9 levels, renal dysfunction, and interstitial fibrosis. The plasma C1q level was significantly decreased, and negatively correlated with urinary protein excretion. Urinary Bb level was a risk factor for no remission (HR = 3.348, 95% CI 1.264-8.870, P = 0.015) and ESRD (HR = 2.323, 95% CI 1.222-4.418, P = 0.010).

Conclusion: In conclusion, our results identified the systemic activation of complement in human primary FSGS, possibly via the classical and alternative pathway. The activation of complement system was partly associated with the clinical manifestations, kidney pathological damage, and renal outcomes.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Plasma and urinary C3a, C5a and soluble C5b-9 levels between patients with primary FSGS and normal subjects.
The plasma and urinary levels of C3a, C5a and C5b-9 were significantly higher in FSGS.
Fig 2
Fig 2. Plasma and urinary C4d, Bb, C1q and MBL levels between patients with primary FSGS and normal subjects.
The plasma C4d level was significantly increased, the plasma C1q level was significantly decreased, and the urinary Bb was significantly increased in FSGS.
Fig 3
Fig 3. Correlations of plasma complement components in each patient.
Plasma level of C4d was positively correlated with that of C3a (A), C5a (B) and C5b-9 (C). Plasma level of Bb was positively correlated with that of C3a (D) and C5b-9 (E).
Fig 4
Fig 4. Correlations of urinary complement components in each patient.
Urinary level of C1q was positively correlated with that of C3a (A), C5a (B) and C5b-9 (C). Urinary level of Bb was positively correlated with that of C3a (D), C5a (E) and C5b-9 (F).
Fig 5
Fig 5. Associations between complement components and clinical-pathologic parameters.
The plasma (A) and urinary (B) levels of soluble C5b-9 were positively correlated with urinary protein excretion. The urinary C5b-9 level was positively correlated with the concentration of serum creatinine (C) and negatively correlated with eGFR (D). The plasma level of C1q was negatively correlated with urinary protein excretion (E) and positively correlated with serum albumin (F). The plasma (G) and urinary (H) level of Bb was positively correlated with serum creatinine. The urinary Bb level was positively correlated with urinary protein (I).
See this image and copyright information in PMC

References

    1. D’Agati V, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011; 365:2398–2411. 10.1056/NEJMra1106556 - DOI - PubMed
    1. D D’Agati V. Pathologic classification of focal segmental glomerulosclerosis. 2003; 23:117–134. 10.1053/snep.2003.50012 - DOI - PubMed
    1. Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011; 17:952–960. 10.1038/nm.2411 - DOI - PMC - PubMed
    1. Huang J, Liu G, Zhang YM, Cui Z, Wang F, Liu XJ, et al. Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis. Kidney Int. 2013; 84:366–372. 10.1038/ki.2013.55 - DOI - PubMed
    1. Huang J, Liu G, Zhang YM, Cui Z, Wang F, Liu XJ, et al. Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis. BMC Med. 2014; 12:81 10.1186/1741-7015-12-81 - DOI - PMC - PubMed

Publication types