Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis

Premkumar Christadoss, Erdem Tüzün, Jing Li, Shamsher S. Saini, Huan Yang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

18 Citations (Scopus)

Abstract

Mice deficient for complement factors C3, C4, or C5 are resistant to experimental autoimmune myasthenia gravis (EAMG). Acetylcholine receptor (AChR) immune lymph node cells (LNC) of C3 deficient mice produce less interleukin 6 (IL-6), and EAMG-resistant IL-6 deficient mice have less serum C3. Increased serum C1q-circulating immune complex (CIC) levels correlated with EAMG disease severity in RIIIS/J mice. The CIC promotes EAMG severity by stimulating the production of LNC IL-6, serum C1q, and C3 via FCγR interaction. Therefore, EAMG/MG could be treated by blocking the activation of classical complement pathway (CCP) and/or IL-6. Anti-C1q antibody administration before and following AChR immunization suppressed EAMG by reducing LNC IL-6 production and neuromuscular junction deposits of IgG, C3, and C5b-C9 complexes. Treatment with low dose (10 μg) of anti-C1q antibody twice a week for 4 weeks in mice with ongoing clinical EAMG reduced the clinical severity of disease and LNC IL-6 production. Therefore, inhibitors of CCP factors C1q, C2, or C4 could treat MG and would preserve the alternate complement pathway activation. Our goal is to tailor MG therapy using anti-C2/C4 reagents in combination, with or without anti-cytokine (e.g., anti-IL-6) reagents.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages210-219
Number of pages10
Volume1132
DOIs
StatePublished - Jun 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1132
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Classical Complement Pathway
Interleukin-6
Lymph Nodes
Cholinergic Receptors
Antigen-Antibody Complex
Anti-Idiotypic Antibodies
Complement C6
Serum
Chemical activation
Immunization
Complement C3
Antibodies
Neuromuscular Junction
Complement Activation
Deposits
Immunoglobulin G
Cytokines

Keywords

  • Autoimmunity
  • Complement
  • Experimental autoimmune myasthenia gravis
  • Immune complex
  • Myasthenia gravis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Christadoss, P., Tüzün, E., Li, J., Saini, S. S., & Yang, H. (2008). Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. In Annals of the New York Academy of Sciences (Vol. 1132, pp. 210-219). (Annals of the New York Academy of Sciences; Vol. 1132). https://doi.org/10.1196/annals.1405.009

Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. / Christadoss, Premkumar; Tüzün, Erdem; Li, Jing; Saini, Shamsher S.; Yang, Huan.

Annals of the New York Academy of Sciences. Vol. 1132 2008. p. 210-219 (Annals of the New York Academy of Sciences; Vol. 1132).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Christadoss, P, Tüzün, E, Li, J, Saini, SS & Yang, H 2008, Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. in Annals of the New York Academy of Sciences. vol. 1132, Annals of the New York Academy of Sciences, vol. 1132, pp. 210-219. https://doi.org/10.1196/annals.1405.009
Christadoss P, Tüzün E, Li J, Saini SS, Yang H. Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. In Annals of the New York Academy of Sciences. Vol. 1132. 2008. p. 210-219. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1405.009
Christadoss, Premkumar ; Tüzün, Erdem ; Li, Jing ; Saini, Shamsher S. ; Yang, Huan. / Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis. Annals of the New York Academy of Sciences. Vol. 1132 2008. pp. 210-219 (Annals of the New York Academy of Sciences).
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