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.
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.
Authors: Regina Maria Papais-Alvarenga; Claudia Cristina Ferreira Vasconcelos; Adriana Carra; Ibis Soto de Castillo; Sara Florentin; Fernando Hamuy Diaz de Bedoya; Raul Mandler; Luiza Campanella de Siervi; Maria Lúcia Vellutini Pimentel; Marina Papais Alvarenga; Marcos Papais Alvarenga; Anderson Kuntz Grzesiuk; Ana Beatriz Calmon Gama Pereira; Antonio Pereira Gomes Neto; Carolina Velasquez; Carlos Soublette; Cynthia Veronica Fleitas; Denise Sisteroli Diniz; Elizabeth Armas; Elizabeth Batista; Freda Hernandez; Fernanda Ferreira Chaves da Costa Pereira; Heloise Helena Siqueira; Hideraldo Cabeça; Jose Sanchez; Joseph Bruno Bidin Brooks; Marcus Vinicius Gonçalves; Maria Cristina Del Negro Barroso; Maria Elena Ravelo; Maria Carlota Castillo; Maria Lúcia Brito Ferreira; Maria Sheila Guimarães Rocha; Monica Koncke Fiuza Parolin; Omaira Molina; Patricia Beatriz Christino Marinho; Paulo Pereira Christo; Renata Brant de Souza; Silvio Pessanha Neto; Solange Maria das Graças Camargo; Suzana Costa Machado; Vanderson Carvalho Neri; Yara Dadalti Fragoso; Helcio Alvarenga; Luiz Claudio Santos Thuler Journal: PLoS One Date: 2015-07-29 Impact factor: 3.240