Related Experiment Video
Updated: Dec 23, 2025

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Complement activation is associated with crescent formation in IgA nephropathy
Hiroe Itami1, Shigeo Hara2, Kenichi Samejima3
1Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, Japan. hritami1237@yahoo.co.jp.
Insights
IgA nephropathy (IgAN) with C3 complement deposits indicates complement pathway activation. This suggests potential therapeutic targets for improving IgAN prognosis.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- IgA nephropathy (IgAN) is a common chronic glomerulonephritis with a variable prognosis.
- Crescent formation in IgAN is linked to poor renal outcomes.
- Complement activation, particularly involving C3, is implicated in IgAN pathogenesis.
Purpose of the Study:
- To investigate the association between C3 deposition and clinical, histological, and immunofluorescence findings in IgAN patients.
- To explore the role of complement activation pathways in IgAN with crescent formation.
Main Methods:
- Retrospective analysis of 132 IgAN patients diagnosed via renal biopsy.
- Classification of patients into groups based on C3 immunofluorescence staining (C≥1 vs. C0).
- Comparison of clinical, light microscopic (including Oxford classification), and immunofluorescence data (IgA, C5b-9, MASP, properdin, factor B, kappa).
Main Results:
- Patients with C3 deposits (C≥1 group) were younger, had lower hypertension rates, and higher urinary abnormalities.
- The C≥1 group showed significantly higher immunofluorescence scores for IgA, C5b-9, MASP-1/3, MASP2, properdin, factor B, and kappa.
- Steroid use was higher in the C≥1 group, and renal dysfunction rates were similar between groups during follow-up.
Conclusions:
- Crescent formation in IgAN is associated with the activation of lectin and alternative complement pathways.
- C3 deposition in IgAN patients correlates with specific immunofluorescence findings and increased steroid treatment.
- Further research into complement-targeted therapies may be beneficial for IgAN management.
Abstract:
IgA nephropathy (IgAN) is common chronic glomerulonephritis with variable prognosis, ranging from minor urinary abnormalities to end-stage renal disease. The revised Oxford classification of IgAN explains that cellular/fibrocellular crescents are associated with poor renal prognosis, proposing an extension to the MEST-C score. C3 immunofluorescent staining follows a distribution similar to IgA staining. Therefore, complement activation was reported to play a pivotal role in IgAN pathogenesis. This study included 132 IgAN patients diagnosed by renal biopsies. The clinical parameters at the time of the biopsies were obtained from patient data records. We classified the patients into C ≥ 1 and C0 groups, and compared clinical, light microscopic, and immunofluorescent features. In the C ≥ 1 group, 2 (1.5%) and 31 (23.5%) patients were assigned to C2 and C1, respectively. The remaining 99 patients (75%) were classified as C0. The C ≥ 1 group had lower average age and rate of hypertension, and higher score of urinary occult blood and E score. The C ≥ 1 group had significantly higher average immunofluorescence scores for IgA, C5b-9, mannose-associated serine protease (MASP) 1/3, MASP2, properdin, factor B, and kappa. The steroid use rate was significantly higher in the C ≥ 1 group. During the follow-up period of 2.90 years on average, the rate of renal dysfunction was not significantly different between groups. Crescent formation in IgAN was associated with activation of the lectin and alternative pathways. The C ≥ 1 group had significantly increased use of steroids, which probably caused comparable renal function during the follow-up period.
More Related Videos
Related Concept Videos
Complement System
Immunoglobulin-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...
Nephrotic Syndrome I : Introduction
Antibody Actions
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Acute Kidney Injury II: Pathophysiology
Transcytosis 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...

