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C5 gene influences the development of murine myasthenia gravis
1Department of Pathology, Burlington 05405.
Abstract:
The influence of the C5 gene and C5 deficiency on murine experimental autoimmune myasthenia gravis (EAMG) susceptibility was evaluated. Two co-isogenic strains, B10.D2/nSn (C5 sufficient) and B10.D2/oSn (C5 deficient), which are genetically identical except for the C5 gene locus, were immunized with acetylcholine receptors (AChR) in CFA to induce myasthenia gravis. Both strains had equivalent concentration of serum autoantibodies to muscle AChR and antibodies bound to muscle AChR. C5-sufficient B10.D2/nSn, but not C5-deficient B10.D2/oSn, demonstrated increased incidence of clinical disease and death and lost significant amounts of muscle AChR. Therefore, C5 deficiency in B10.D2/oSn prevented EAMG. C5 gene, which codes for C component C5, may influence EAMG pathogenesis through activation of the terminal lytic C sequence (C5 to C9) required for muscle AChR destruction, which is the primary pathology.
Insights
Complement C5 deficiency prevents experimental autoimmune myasthenia gravis (EAMG) in mice. C5-sufficient mice developed EAMG, while C5-deficient mice were protected, indicating C5
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Experimental autoimmune myasthenia gravis (EAMG) is an autoimmune disorder affecting neuromuscular junctions.
- The complement system, particularly C5, plays a role in inflammatory and autoimmune diseases.
Purpose of the Study:
- To investigate the role of the C5 gene and C5 deficiency in EAMG susceptibility.
- To determine if C5 is essential for the development of EAMG.
Main Methods:
- Utilized two co-isogenic mouse strains: B10.D2/nSn (C5 sufficient) and B10.D2/oSn (C5 deficient).
- Induced EAMG by immunizing mice with acetylcholine receptors (AChR) in Complete Freund's Adjuvant (CFA).
- Assessed clinical disease incidence, mortality, serum autoantibodies to AChR, and AChR binding to muscle.
Main Results:
- Both C5-sufficient and C5-deficient mice produced equivalent levels of anti-AChR antibodies.
- C5-sufficient mice exhibited a higher incidence of clinical EAMG, mortality, and significant loss of muscle AChR.
- C5-deficient mice were protected from developing clinical EAMG and muscle AChR destruction.
Conclusions:
- C5 deficiency prevents the development of EAMG in a murine model.
- The C5 component of the complement system is crucial for EAMG pathogenesis, likely through the terminal lytic pathway (C5-C9) mediating muscle AChR destruction.