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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
Absence of functional alternative complement pathway alleviates lupus cerebritis
Jessy J Alexander1, Alexander Jacob, Paul Vezina
1Department of Medicine, University of Chicago, Chicago, IL 60637, USA. jalexand@medicine.bsd.uchicago.edu
European Journal of Immunology
|May 25, 2007
Summary
The alternative complement pathway contributes to lupus cerebritis. Blocking this pathway with complement factor B deficiency reduced neuroinflammation and improved behavioral outcomes in lupus model mice.
Area of Science:
- Immunology
- Neuroscience
- Rheumatology
Background:
- The complement system, particularly the alternative pathway, plays a role in CNS diseases like lupus cerebritis.
- Understanding the specific contribution of the alternative pathway is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of the alternative complement pathway in lupus cerebritis using mice deficient in complement factor B (fB).
Main Methods:
- Studied MRL/lpr mice with and without complement factor B (fB-/-MRL/lpr vs. MRL/lpr).
- Assessed immune deposits, neutrophil infiltration, apoptosis, protein expression (p-Akt, p-PTEN), extracellular matrix components, and behavioral alterations.
Main Results:
- fB deficiency reduced immune deposits, neutrophil infiltration, and apoptosis in the brain.
- Absence of fB increased p-Akt and decreased p-PTEN expression, suggesting neuroprotection.
- Tissue integrity was maintained, and behavioral deficits were reduced in fB-deficient mice.
Conclusions:
- The alternative complement pathway is a key driver of CNS inflammation in lupus.
- Targeting the alternative pathway, specifically complement factor B, may be a promising therapeutic strategy for lupus cerebritis.
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