Related Experiment Video
Updated: Oct 18, 2025
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Complement Activation Is Associated With Crescents in IgA Nephropathy
Zi Wang1,2,3, Xinfang Xie1,2,3, Jingyi Li1,2,3
1Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
Insights
Excess complement activation, particularly involving mannose-binding lectin (MBL) and C4d, is linked to crescent formation in IgA nephropathy (IgAN). Urinary C4d levels correlate with crescent proportion, serving as a potential biomarker for monitoring kidney disease progression.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Crescents in IgA nephropathy (IgAN) are associated with rapid kidney disease progression.
- The precise mechanisms driving crescent formation in IgAN remain incompletely understood.
- Investigating the role of complement system overactivation is crucial for understanding IgAN pathogenesis.
Purpose of the Study:
- To determine if excessive complement activation contributes to crescent formation in IgAN patients.
- To evaluate the association between urinary complement markers and the proportion of crescents.
- To assess the predictive value of complement activation markers for renal survival in IgAN.
Main Methods:
- One hundred IgAN patients were categorized based on crescent percentage (0% to >75%).
- Urinary levels of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were quantified.
- Immunohistochemistry was used to assess glomerular C4d, C5b-9, and C3d deposition; ROC curves analyzed predictive abilities.
Main Results:
- Patients with >50% crescents exhibited significantly higher urinary C3a/Cr, C5a/Cr, and sC5b-9/Cr levels (p<0.001).
- Urinary MBL and C4d levels showed a linear correlation with the proportion of crescents (r=0.457 and r=0.562, respectively; p<0.001).
- Glomerular C4d deposition increased proportionally with crescent formation; combined urinary complement markers showed borderline improved prediction of renal survival.
Conclusions:
- Excessive complement activation, particularly the lectin pathway, is implicated in crescent formation in IgAN.
- Urinary C4d levels correlate with crescent proportion and may serve as a biomarker for monitoring disease activity.
- These findings highlight complement activation as a key factor in the pathogenesis of crescentic IgAN.
Introduction:
Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.
Methods:
One hundred IgAN patients with various proportions of crescents-24 with 1%-24%, 27 with 25%-49%, 21 with 50%-74% 12 with more than 75%, and 16 without crescents-were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.
Results:
IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652-62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0-1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127-66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859-2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058-1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916-11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.
Conclusion:
Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.
More Related Videos
09:43Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
14:18Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
Related Concept Videos
01:27Complement System
01:24Nephrotic Syndrome I : Introduction
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:17Gastritis-II: Pathophysiology
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
01:15Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
01:20Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...