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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
Complement in lupus nephritis: the good, the bad, and the unknown
1Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. lbao@medicine.bsd.uchicago.edu
Seminars in Nephrology
|March 6, 2007
Summary
The complement system plays a dual role in systemic lupus erythematosus (SLE). While early complement proteins are protective, later activation is harmful, offering therapeutic targets for SLE.
Area of Science:
- Immunology
- Rheumatology
Background:
- The complement system, comprising over 30 proteins and 3 pathways, regulates immune responses but can paradoxically contribute to disease.
- Hereditary deficiencies in early complement components increase SLE risk, yet complement activation is evident in active disease.
- Mouse models have been crucial for understanding SLE pathogenesis and testing complement-targeted therapies.
Purpose of the Study:
- To elucidate the complex role of the complement system in systemic lupus erythematosus (SLE) pathogenesis.
- To investigate the protective versus proinflammatory functions of different complement pathway components.
- To evaluate the therapeutic potential of complement inhibitors in SLE.
Main Methods:
- Utilized genetically modified mouse models of SLE to study complement's role.
- Examined the effects of early complement proteins (C1q, C4) and later pathway activation.
- Assessed the safety and efficacy of complement inhibitors like soluble complement receptor 1 and anti-C5 antibody.
Main Results:
- Confirmed that early complement proteins (C1q, C4) are protective in SLE.
- Demonstrated that complement activation later in the cascade is proinflammatory and detrimental.
- Identified complement inhibitors (TP10, Eculizumab) that safely modulate complement activity.
Conclusions:
- The complement system's role in SLE is complex, with early components being protective and later activation being pathogenic.
- Complement inhibitors show promise for treating lupus nephritis, but clinical trials face challenges.
- Targeting specific complement pathways offers a potential therapeutic strategy for SLE management.
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