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Antiacquaporin 4 antibodies detection by different techniques in neuromyelitis optica patients

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

ML Malosio

Immunology of Diabetes Unit, San Raffaele Scientific Institute, Milan, Italy

V. Lampasona

Human Molecular Genetics Unit, San Raffaele Scientific Institute, Milan, Italy

D. De Feo

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

D. Privitera

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

F. Marnetto

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Turin, Italy

D. Centonze

Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy

A. Ghezzi

Ospedale di Gallarate, Centro Studi Sclerosi Multipla, Gallarate, Varese, Italy

G. Comi

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

R. Furlan

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy, furlan.roberto{at}hsr.it

G. Martino

Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

Background: Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as a marker for the diagnosis of neuromyelitis optica (NMO). However, a consensus on seroprevalence and optimal detection method has not yet been reached.

Objectives: To investigate the performance of different assays to detect anti-AQP4 antibodies.

Methods: We set up five different assays. Two of them were capable to detect perivascular IgG reactivity on brain tissue by immunofluorescence (NMO-IgG). Other three assays have been set to detect anti-AQP4 antibodies: immunofluorescence and flow cytometry on AQP4-expressing cells, and a radioimmunoprecipitation assay. We assessed sensitivity and specificity of these assays by interrogating sera of 33 NMO patients, 13 patients at high risk to develop NMO (hrNMO), 6 patients affected by acute partial transverse myelitis (APTM), 20 patients with multiple sclerosis (MS), and 67 age- and sex-matched healthy controls.

Results: We found that the presence of serum NMO-IgG and anti-AQP4 reactivity is almost exclusively restricted to patients with NMO and hrNMO. Seroprevalence and sensitivity ranged from 30 to 47%, depending on the assay. Specificity ranged from 95 to 100%. Comparing results obtained in the five assays, we noticed lack of concordance in some samples.

Conclusions: Detection of NMO-IgG or anti-AQP4 antibodies may represent a valuable tool to assist neurologists in the differential diagnosis between patients with NMO, hrNMO, APTM, or MS. The current lack of a gold standard to detect anti-AQP4 antibodies implies the necessity to standardize the detection of these antibodies.

Key Words: Neuromyelitis optica

This version was published on October 1, 2009

Multiple Sclerosis, Vol. 15, No. 10, 1153-1163 (2009)
DOI: 10.1177/1352458509106851


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