Targeting classical complement pathway to treat complement mediated autoimmune diseases

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

Research output: Chapter in Book/Report/Conference proceedingChapter

12 Scopus citations

Abstract

Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). Anti-C1q antibody administration before or following acetylcholine receptor immunization suppresses EAMG development by reducing lymph node cell IL-6 production and neuromuscular junction IgG, C3 and C5b-C9 deposition. This effect is achieved by treating mice with 10 μg of anti-C1q antibody, twice weekly for 4 weeks. Treatment with a higher amount of anti-C1q antibody gives rise to increased serum anti-acetylcholine receptor antibody, immune complex and C3 levels, facilitates kidney C3 and IgG deposits and thus reduces the treatment efficacy. C4 KO and anti-C1q antibody treated mice display normal immune system functions and intact antibody production capacity. Furthermore, CCP inhibition preserves alternative complement pathway activation, which is required for host defense against microorganisms. Therefore, CCP inhibition might constitute a specific treatment approach for not only myasthenia gravis but also other complement mediated autoimmune diseases.

Original languageEnglish (US)
Title of host publicationCurrent Topics in Complement II
EditorsJohn Lambris
Pages265-272
Number of pages8
StatePublished - Dec 1 2008

Publication series

NameAdvances in Experimental Medicine and Biology
Volume632
ISSN (Print)0065-2598

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tüzün, E., Li, J., Saini, S. S., Yang, H., & Christadoss, P. (2008). Targeting classical complement pathway to treat complement mediated autoimmune diseases. In J. Lambris (Ed.), Current Topics in Complement II (pp. 265-272). (Advances in Experimental Medicine and Biology; Vol. 632).