AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance

Nat Rev Neurol. 2010 Jul;6(7):383-92. doi: 10.1038/nrneurol.2010.72.


Antibodies to aquaporin-4 (also known as AQP4-Ab or NMO-IgG) are sensitive and highly specific serum markers of autoimmune neuromyelitis optica (NMO). Second-generation recombinant diagnostic assays can detect AQP4-Ab in >or=80% of patients with NMO, and a role for AQP4-Ab in the pathophysiology of this condition was corroborated by a series of in vitro studies that demonstrated disruption of the blood-brain barrier, impairment of glutamate homeostasis and induction of necrotic cell death by AQP4-Ab-positive serum. Additional evidence for such a role has emerged from clinical observations, including the demonstration of a correlation between serum levels of AQP4-Ab and disease activity. The finding of NMO-like CNS lesions and clinical disease following passive transfer of AQP4-Ab-positive serum in several independent animal studies provided definitive proof for a pathogenic role of AQP4-Ab in vivo. Together, these findings provide a strong rationale for the use of therapies targeted against B cells or antibodies in the treatment of NMO. In this Review, we summarize the latest evidence in support of a direct involvement of AQP4-Ab in the immunopathogenesis of NMO, and critically appraise the diagnostic tests currently available for the detection of this serum reactivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies / analysis
  • Antibodies / immunology*
  • Aquaporin 4 / immunology*
  • Biomarkers
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / physiology
  • Glucose / metabolism
  • Homeostasis / physiology
  • Humans
  • Neuromyelitis Optica / diagnosis
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / therapy*
  • Predictive Value of Tests
  • Treatment Outcome


  • AQP4 protein, human
  • Antibodies
  • Aquaporin 4
  • Biomarkers
  • Glucose