AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance.
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.
Jarius
Sven
S
Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Wildemann
Brigitte
B
D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D051401:Aquaporin 4 / Q000276:immunology*; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000276:immunology / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
C496030:AQP4 protein, human; D000906:Antibodies; D051401:Aquaporin 4; D015415:Biomarkers; D005947:Glucose