NMO spectrum disorders and anti AQP4 antibody

Yoshiki Takai, Tatsuro Misu, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The proposed relationship between NMO and multiple sclerosis (MS) has long been controversial. However, after the discovery of an NMO-specific antibody against aquaporin-4 (AQP4), a water channel mainly expressed in astrocytes, clinical, MRI, and laboratory features, including longitudinally extensive spinal cord lesions and unique brain lesions, were identified in NMO. Analyses of AQP4 antibody-positive cases have shown that the clinical spectrum of NMO is wider than just optic myelitis. Neuropathological studies have demonstrated extensive loss of AQP4 and glial fibrillary acidic protein (GFAP) in NMO lesions, especially in perivascular areas of acute inflammatory lesions where immunoglobulins and activated complements are deposited. In contrast, myelin basic protein (MBP)-positive myelinated fibers are relatively preserved, suggesting that myelin damage is secondary to astrocyte destruction. The GFAP level in the cerebrospinal fluid is remarkably elevated during relapse of NMO, but not in MS. Experimental studies strongly suggest that AQP4 antibodies are pathogenic; they activate complements and destroy AQP4-expressing cells. Between two AQP4 isoforms, M1 and M23, AQP4 antibody has a higher affinity to M23 because it forms an orthogonal array of particles that appears to be specifically recognized by AQP4 antibodies. Immunosuppression is the mainstay of NMO management. High-dose intravenous methylprednisolone and plasma exchange are employed during acute exacerbation, and corticosteroids and immunosuppressants are efficacious in reducing NMO relapse. Importantly, some disease-modifying drugs for MS, such as interferon-beta and fingolimod, can exacerbate NMO; therefore, early differentiation between NMO and MS is important in selecting an appropriate treatment strategy. In conclusion, NMO is now classified as an autoimmune astrocytopathic disease targeting AQP4, rather than a demyelinating disease like MS. Further studies are warranted to clarify disease pathogenesis and develop a molecular target treatment for NMO.

Original languageEnglish
Pages (from-to)333-343
Number of pages11
JournalBrain and Nerve
Issue number4
Publication statusPublished - 2013 Apr


  • Aquaporin-4 (AQP4)
  • Multiple sclerosis
  • Neuromyelitis optica (NMO)
  • NMO-IgG
  • NMOsd


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