In other diseases with less antigen-specificity, such as rheumatoid arthritis and multiple sclerosis, there is significant heterogeneity in the immunodominant antigen responses; in contrast, NMO is defined by reaction primarily to the AQP4 water channel although the precise target within AQP4 may vary slightly among NMO patients with some patients producing antibody responses against loops A and E as well [19]. Here, AQP4 is linked to multiple sclerosis.