AQP4 and neuromyelitis optica: Indirect evidence suggesting that serum NMO-IgG is pathogenic includes the high specificity of NMO-IgG seropositivity for NMO [1], correlations between serum NMO-IgG titers and disease activity [13], [14], loss of AQP4 in NMO lesions [15], and the clinical benefit of NMO-IgG depletion by plasma exchange [16].