Advancing Treatment for C3G; Targeting the Complement System for Personalized Kidney Care - Episode 1
Understanding C3G: Pathophysiology and Genetic Factors
Panelists discuss how C3 glomerulopathy is an ultrarare glomerular disease characterized by alternative pathway complement dysregulation, which can be caused by either genetic defects or acquired abnormalities like antibodies against regulatory proteins.
Video content above is prompted by the following:
C3 Glomerulopathy: Pathophysiology Summary
This summary provides an overview of C3 glomerulopathy (C3G) pathophysiology as described by Jonathan Barratt, MBChB, PhD, FRCP,
during a clinical discussion.
Disease Classification
- C3G is an ultrarare glomerular disease
- Primary disorder of the alternative pathway of complement activation and regulation
Pathophysiological Mechanisms
C3G can be driven by 2 main mechanisms:
- Genetic basis:
- Gain-of-function mutations leading to easier complement system activation
- Loss of function in key complement regulatory proteins that normally restrict alternative pathway activation
- Acquired basis:
- Antibodies (nephritic factors) that bind to convertase enzymes, preventing proper deactivation
- Antibodies against regulatory proteins that inhibit their function
- Monoclonal proteins (in monoclonal gammopathy of renal significance) that block regulatory pathways
Diagnostic Features
- Kidney biopsy reveals excess C3 complement protein within glomeruli
- Characteristic absence of immunoglobulins or immune complexes
- Evidence of unilateral alternative pathway complement activation driving glomerular injury
This understanding of C3G pathophysiology highlights the importance of differentiating between acquired and genetic complement abnormalities for proper diagnostic classification and therapeutic approach.
