Complement associated pathogenic mechanisms in myasthenia gravis

Tuzun E., CHRISTADOSS P.

AUTOIMMUNITY REVIEWS, cilt.12, sa.9, ss.904-911, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 12 Sayı: 9
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.autrev.2013.03.003
  • Dergi Adı: AUTOIMMUNITY REVIEWS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.904-911
  • Anahtar Kelimeler: Myasthenia gravis, Experimental autoimmune myasthenia gravis, Complement, Classical pathway, Autoimmunity, DECAY-ACCELERATING FACTOR, NEUROMUSCULAR-JUNCTION, IMMUNE-COMPLEXES, MOTOR ENDPLATE, ACETYLCHOLINE-RECEPTORS, AUTOIMMUNE-DISEASE, EXTRAOCULAR-MUSCLE, SERUM COMPLEMENT, PASSIVE TRANSFER, MOUSE MODEL
  • İstanbul Üniversitesi Adresli: Evet

Özet

The complement system is profoundly involved in the pathogenesis of acetylcholine receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). The most characteristic finding of muscle pathology in both MG and EAMG is the abundance of IgG and complement deposits at the nerve-muscle junction (NMJ), suggesting that AChR-Ab induces muscle weakness by complement pathway activation and consequent membrane attack complex (MAC) formation. This assumption has been supported with EAMG resistance of complement factor C3 knockout (KO), C4 KO and C5 deficient mice and amelioration of EAMG symptoms following treatment with complement inhibitors such as cobra venom factor, soluble complement receptor 1, anti-C1q, anti-C5 and anti-C6 Abs. Moreover, the complement inhibitor decay accelerating factor (DAF) KO mice exhibit increased susceptibility to EAMG. These findings have brought forward improvisation of novel therapy methods based on inhibition of classical and common complement pathways in MG treatment. (C) 2013 Elsevier B.V. All rights reserved.