Newest Immunotherapies in NMOSD: Which One to Choose?

Aquaporin-4 autoantibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disease (NMOSD) is a relapsing autoimmune central nervous system disorder that results in significant permanent neurologic disability1. Histopathology, experimental animal models, and human translational studies have illuminated immune cell populations, cytokines, and effector mechanisms that impact NMOSD CNS lesion formation.2-5AQP4-IgG produced by terminally differentiated antibody producing cells (plasmablasts and plasma cells) binds to CNS astrocytes and initiates injury through multiple mechanisms including complement-mediated cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and AQP4 internalization. CDC directly damages target astrocytes, and nearby oligodendrocytes and neurons, recruits and activates peripheral immune cells, degranulates polymorphonuclear cells, and enhances blood-brain barrier (BBB) permeability. Interleukin-6, a pleiotropic cytokine, is elevated in NMOSD patient serum and cerebrospinal fluid (CSF) and may facilitate plasmablast survival, pro-inflammatory IL-17+ T cell differentiation, BBB leakage, and microglial activation.5 In addition to their production of AQP4-IgG, B cells may also modulate disease activity through antigen presentation and pro-inflammatory and regulatory cytokine secretion.