Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica.

Anti-aquaporin 4 antibodies (AQP4-Ab) are specifically detected in patients with neuromyelitis optica. To investigate the role of AQP4-Ab, we examined the antibody binding epitope using human and mouse mutant AQP4.We constructed human and mouse amino acid substitution AQP4 mutants and compared the reactivity with wild-form of human, mouse and rat AQP4.The decreased intensity of AQP4-Ab staining with mouse AQP4 was recovered to that of human AQP4 with the mouse mutant A228E for 9 of the 10 sera.The third extracellular loop of AQP4 is considered to be the major epitope for AQP4-Ab in NMO.