Complement C2 siRNA mediated therapy of myasthenia gravis in mice

Ruksana Huda, Erdem Tüzün, Premkumar Christadoss

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Activation of complement components is crucial in the progression and severity of myasthenia gravis and experimental autoimmune myasthenia gravis (EAMG). Mice deficient in complement component C4 or treated with monoclonal antibody to C1q are resistant to EAMG. In this study, we show that inhibition of complement cascade activation by suppressing the expression of a critical low-abundant protein, C2, in the classical complement pathway, significantly improved clinical and immunopathological manifestations of EAMG. Two weeks after a second booster immunization with acetylcholine receptor, when mice exhibit muscle weakness, i.p. injection of C2 siRNA significantly suppressed C2 mRNA in the blood cells and liver of EAMG mice. Treatment of EAMG mice with C2 siRNA, once a week for 5 weeks, significantly improved muscle strength, which was further evidenced by functional AChR preservation in muscle, reduction in number of C3 and membrane-attack complexes at neuro-muscular junctions in forelimb muscle sections, and a transient decrease in serum IgG2b levels. Our study shows for the first time that siRNA-mediated suppression of C2, a component of the classical complement system, following established disease, can effectively contribute to the remission of EAMG. Therefore, C2 siRNA mediated therapy can be applied in all complement mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)94-104
Number of pages11
JournalJournal of Autoimmunity
Volume42
DOIs
StatePublished - May 2013

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Autoimmune Experimental Myasthenia Gravis
Complement C2
Myasthenia Gravis
Small Interfering RNA
Complement Activation
Therapeutics
Classical Complement Pathway
Complement C4
Complement Membrane Attack Complex
Secondary Immunization
Muscles
Forelimb
Muscle Weakness
Muscle Strength
Cholinergic Receptors
Autoimmune Diseases
Blood Cells
Monoclonal Antibodies
Messenger RNA
Injections

Keywords

  • Autoimmunity
  • C2 siRNA
  • Classical pathway
  • Complement
  • Experimental autoimmune myasthenia gravis
  • Myasthenia gravis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Complement C2 siRNA mediated therapy of myasthenia gravis in mice. / Huda, Ruksana; Tüzün, Erdem; Christadoss, Premkumar.

In: Journal of Autoimmunity, Vol. 42, 05.2013, p. 94-104.

Research output: Contribution to journalArticle

Huda, Ruksana ; Tüzün, Erdem ; Christadoss, Premkumar. / Complement C2 siRNA mediated therapy of myasthenia gravis in mice. In: Journal of Autoimmunity. 2013 ; Vol. 42. pp. 94-104.
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