Classical complement pathway in experimental autoimmune myasthenia gravis pathogenesis


CHRISTADOSS P., Tuzun E., LI J., SAINI S. S., YANG H.

MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE, cilt.1132, ss.210-219, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1132
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1196/annals.1405.009
  • Dergi Adı: MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.210-219
  • Anahtar Kelimeler: myasthenia gravis, experimental autoimmune myasthenia gravis, complement, immune complex, autoimmunity, CIRCULATING IMMUNE-COMPLEXES, T-CELL PROLIFERATION, ACETYLCHOLINE-RECEPTOR, ETANERCEPT TREATMENT, ANTI-C1Q ANTIBODY, GENETIC-EVIDENCE, MUSCLE-CELLS, IFN-GAMMA, B-CELL, MICE
  • İstanbul Üniversitesi Adresli: Hayır

Özet

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 Clq-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 FC gamma R 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 mu g) 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.