Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.
Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy.
Departments of Laboratory Medicine/Pathology and Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
Shannon R
SR
Hinson
Departments of Laboratory Medicine/Pathology and Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
Vanda A
VA
Lennon
Departments of Laboratory Medicine/Pathology and Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA. Electronic address: pittock.sean@mayo.edu.
Sean J
SJ
Pittock
D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000378:metabolism*; D053447:Channelopathies / Q000150:complications* / Q000378:metabolism; D050581:Excitatory Amino Acid Transporter 4 / Q000276:immunology; D006801:Humans; D009471:Neuromyelitis Optica / Q000150:complications* / Q000378:metabolism; D039781:PubMed / Q000706:statistics & numerical data
D051401:Aquaporin 4; D001323:Autoantibodies; D050581:Excitatory Amino Acid Transporter 4; C493391:SLC1A6 protein, human
AQP4; EAAT2; astrocyle; demyelination; multiple sclerosis; neuromyelitis optica; optic neuritis; transverse myelitis; water channel