Anti-C5 antibody treatment ameliorates weakness in experimentally acquired myasthenia gravis.

Abstract

Myasthenia gravis (MG) is a neuromuscular transmission disorder in which damage to acetylcholine receptors (AChR) on motor endplates by autoantibody-induced complement attack causes muscle weakness. To determine whether and, if so, to what extent, blockade of complement cascade at the C5 step ameliorates disease, we evaluated the effect of administering a functionally blocking anti-C5 mAb in passive experimental MG in Lewis rats induced with AChR Ab McAb-3. In contrast to uniform severe weakness at 24 h requiring euthanasia in untreated animals, anti-C5 mAb-pretreated rats showed no weakness at 48 h. Anti-C5 mAb treatment 24 h after disease induction restored strength in two-thirds of the rats. Immunofluorescence staining of endplates from the treated animals showed that C9 deposition at AChR was reduced and ultrastructural analyses showed that endplates were intact. The results argue that targeting C5 may warrant testing in MG patients and that this approach may be particularly valuable for myasthenic crisis.

• Authors: Yuefang Zhou, Bendi Gong, Feng Lin, Russell P Rother, M Edward Medof, Henry J Kaminski
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 179 Issue 12 Pg. 8562-7 (Dec 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 18056404 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Cholinergic Antagonists
• Complement C5
• Complement C9
• Receptors, Cholinergic

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Cholinergic Antagonists (pharmacology)
• Complement C5 (analysis, antagonists & inhibitors)
• Complement C9 (metabolism)
• Female
• Muscle Weakness (drug therapy, pathology)
• Myasthenia Gravis, Autoimmune, Experimental (drug therapy, pathology, prevention & control)
• Neuromuscular Junction (drug effects)
• Rats
• Rats, Inbred Lew
• Receptors, Cholinergic (drug effects)