C5a is not involved in experimental autoimmune myasthenia gravis pathogenesis

Abstract

C5 deficient mice are highly resistant to experimental autoimmune myasthenia gravis (EAMG) despite intact immune response to acethylcholine receptor (AChR), validating the pivotal role played by membrane attack complex (MAC, C5b-9) in neuromuscular junction destruction. To distinguish the significance of C5a from that of C5b in EAMG pathogenesis, C5a receptor (C5aR) knockout (KO) and wild-type (WT) mice were immunized with AChR to induce pathogenic antiAChR antibodies. In contrast with C5 deficient mice, C5aR KO mice were equally susceptible to EAMG as WT mice and exhibited comparable antibody and lymphocyte proliferation response to AChR implicating that C5a is not involved in EAMG development.

Myeloid-Derived Suppressor Cells as a Potential Therapy for Experimental Autoimmune Myasthenia Gravis

“…Following previously published protocols (13, 16, 17), we induced EAMG in WT C57BL/6 mice by repeated immunization with AChR in complete Freund's adjuvant. One week after the boost, we evaluated muscle strength of the immunized mice using a grid-hanging method and measured sera AChR-specific IgG levels by ELISA to confirm the establishment of EAMG.…”

Complement and cytokine based therapeutic strategies in myasthenia gravis

“…While C5b is a component of the MAC, C5a is an anaphylactic and chemotactic agent, which mediates various immunological functions such as production of cytokines IL-1b, IL-6 and TNF-a that are actively involved in EAMG pathogenesis [29]. Nevertheless, AChR-immunized C5aR KO and WT mice show identical EAMG incidences, clinical scores, grip strengths, AChR antibody levels and NMJ complement deposit counts [30], suggesting that C5a is not involved in NMJ AChR loss and C5 deficiency or inhibition prevents EAMG induction through impaired MAC production due to lack of the C5b component.…”

Myasthenia gravis: the role of complement at the neuromuscular junction

“…It is possible that the absence of C5a may have contributed to the lower incidence of EAMG observed in C5‐deficient mice than in wild‐type animals . However, a study comparing C5a gene knockout and wild‐type mice showed that both types of mice were equally susceptible to the development of EAMG by AChR immunization . Assessments of muscle strength were similar in the two groups, and both groups showed similar levels of serum anti‐AChR antibodies and amounts of IgG, C3, and MAC deposited at the NMJ.…”