Fig. 1.

Main pathogenic mechanism by which AQP4-IgG causes NMOSD. 1 — B cells differentiate into AQP4-IgG-secreting plasmablasts which is helped by interleukin-6; 2 — AQP4-IgG enters the circulation and traverses the blood–brain barrier; 3 — AQP4-IgG binds to AQP4 on the surface of astrocytes; 4 — C1q binds to AQP4-IgG and activates the classical complement pathway; 5 — astrocyte damage occurs from opsonization with complement and formation of the membrane attack complex (c5–c9); 6 — C5a is an anaphylatoxin and recruits granulocytes; 7 — granulocytes damage neurons and oligodendrocytes; 8 — the end result is demyelination