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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
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Urine Proteomics Link Complement Activation with Interstitial Fibrosis/Tubular Atrophy in Lupus Nephritis Patients
Shudan Wang1, Anna Broder2, Daming Shao3
1Division of Rheumatology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Seminars in Arthritis and Rheumatism
|October 6, 2023
Summary
Complement activation markers, including urinary C3, CFI, and the C9-to-CD59 ratio, are associated with tubulointerstitial fibrosis in lupus nephritis (LN). These findings suggest potential biomarkers for assessing kidney fibrosis severity in LN patients.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Intrarenal complement activation is implicated in lupus nephritis (LN) pathogenesis.
- The membrane attack complex (MAC) formation and its inhibition by CD59 play roles in kidney damage.
- An imbalance between complement activation and inhibition may drive interstitial fibrosis and tubular atrophy (IFTA) in LN.
Purpose of the Study:
- To investigate the association between urinary complement components and IFTA in LN patients.
- To determine if the urinary C9-to-CD59 ratio correlates with IFTA severity.
- To explore the relationship between complement activation markers and key mediators of kidney fibrosis.
Main Methods:
- Analysis of urine samples from 46 biopsy-proven LN patients.
- Comparison of urinary complement components and C9-to-CD59 ratio between patients with moderate/severe vs. none/mild IFTA.
- Proteomics analysis using mass spectrometry and correlation with fibrosis mediators (TGFβR1, TGFβR2, PDGFβ, PDGFRβ).
Main Results:
- LN patients with moderate/severe IFTA showed an increased urinary C9-to-CD59 ratio (p=0.01).
- Higher urinary C3 (p=0.02) and CFI (p=0.01) levels were observed in patients with moderate/severe IFTA.
- Complement components (C3, C9, CD59, CFI) correlated with fibrosis-related factors (TGFβR1, TGFβR2, PDGFβ, PDGFRβ).
Conclusions:
- Urinary C3, CFI, and the C9-to-CD59 ratio are potential biomarkers for tubulointerstitial fibrosis in LN.
- This study provides insights into the role of complement dysregulation in LN-associated kidney fibrosis.
- Findings highlight the potential of urinary complement profiling for assessing LN progression.
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