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  • Review Article
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AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance

Nature Reviews Neurology volume 6, pages 383–392 (2010)Cite this article

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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.

Key Points

  • Growing evidence implicates aquaporin-4 antibody (AQP4-Ab)-mediated autoimmunity in the pathogenesis of neuromyelitis optica (NMO) and its formes frustes, but not in multiple sclerosis or other CNS autoimmune conditions

  • Robust evidence for a direct involvement of AQP4-Ab in NMO immunopathogenesis comes from animal studies reporting NMO-like disease after passive transfer of AQP4-Ab-positive human serum

  • A strong rationale exists for the use of therapies targeting B cells or antibodies in NMO, and this will be an important consideration for future treatment trials

  • Second-generation recombinant serological assays with higher sensitivity and specificity than the original 'NMO-IgG' test are now available and should be offered to all patients with NMO or related disorders

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Figure 1: Histopathological findings in NMO, MS and EAE.
Figure 2: Ribbon diagrams of a human AQP4 homotetramer.
Figure 3: Freeze fracture images showing the plasma membrane of CHO cells.
Figure 4: Detection of AQP4-Ab by indirect immunofluorescence techniques.

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Acknowledgements

The work of S. Jarius was supported by a Research Fellowship from the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS).

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  1. Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Sven Jarius & Brigitte Wildemann

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The authors have received research grants from Bayer Schering Pharma and Merck Serono. The funding sources had no role in data collection, analysis of data, preparation of the manuscript, or decision to publish this Review.

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Jarius, S., Wildemann, B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 6, 383–392 (2010). https://doi.org/10.1038/nrneurol.2010.72

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