Thus the binding of human NMO-IgG to murine AQP4 suggests at least three interpretations: 1) that Loop A is not a B cell epitope, 2) the changes between rodents and humans do not affect antibody binding if the loop A sequence is a B cell epitope., or 3) the sequence changes do affect binding of anti-AQP4 antibodies, but other AQP4 epitopes are still available and antibodies in polyclonal sera have enough reactivity to AQP4 to be scored as positive for binding if one AQP4 epitope is compromised. This evidence concerns the gene AQP4 and neuromyelitis optica.