Establishment of monoclonal antibodies against the extracellular domain that block binding of NMO-IgG to AQP4

• Epitopes of NMO-IgG were varied, though they were restricted to AQP4-EC domains.
• High affinity mAbs against AQP4-EC domains were developed by baculovirus display.
• Established mAbs displaced NMO-IgGs from cells expressing hAQP4.
• Antagonistic effect of these mAbs can be a new therapeutic option for NMO.

Neuromyelitis optica is a demyelinating disease characterized by a disease-specific autoantibody designated as NMO-IgG that specifically recognizes aquaporin-4, and the binding of NMO-IgG to AQP4 causes the progress of the disease. Prevention of the binding of NMO-IgG, therefore, may alleviate the disease. Here we have developed monoclonal antibodies against AQP4 with a baculovirus display system in order to obtain high affinity monoclonal antibodies against the extracellular domains of AQP4. Our monoclonal antibodies can block the binding of NMO-IgG in spite of their heterogeneity. Taken together, we propose that our monoclonal antibodies can be applied in clinical therapy for NMO patients.