AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance.

Nature Reviews. Neurology
Sven Jarius, Brigitte Wildemann

Abstract

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 ...Continue Reading

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