AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance

S Jarius, B Wildemann - Nature Reviews Neurology, 2010 - nature.com
S Jarius, B Wildemann
Nature Reviews Neurology, 2010nature.com
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≥ 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 …
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 ≥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.
nature.com