This again draws parallels to the structural requirements promoting binding of AQP4-IgG to AQP4 tetramers and orthogonal arrays in NMO (53, 54), in which the assembly of multimeric rAb clusters on complex AQP4 orthogonal arrays drives C1q binding and activation of the classical complement pathway (55). This evidence concerns the gene AQP4 and neuromyelitis optica.