期刊论文详细信息
Journal of Neuroinflammation
Aquaporin-4 antibody testing: direct comparison of M1-AQP4-DNA-transfected cells with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate
Brigitte Wildemann6  Orhan Aktas7  Florence Pache1  Marius Ringelstein7  Diego Franciotta3  Ingo Kleiter8  Klemens Ruprecht2  Kai Fechner4  Friedemann Paul1  Sven Jarius5 
[1] Department of Neurology Charité-Universitätsmedizin, NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Berlin, Germany;Department of Neurology, Charité University Medicine, Berlin, Germany;IRCCS, C. Mondino National Neurological Institute, Pavia, Italy;Institute for Experimental Immunology, affiliated to Euroimmun AG, Luebeck, Germany;Molecular Neuroimmunology, Department of Neurology, Otto Meyerhof Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany;Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany;Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany;Department of Neurology, University of Bochum, Bochum, Germany
关键词: optica neuritis;    longitudinally extensive transverse myelitis;    antibody testing;    M23 aquaporin-4;    M1 aquaporin-4;    cell-based assay;    antibodies to aquaporin-4;    NMO-IgG;    Devic’s syndrome;    Devic syndrome;    neuromyelitis optica spectrum disorders;    neuromyelitis optica;   
Others  :  1228268
DOI  :  10.1186/1742-2094-11-129
 received in 2014-03-19, accepted in 2014-07-08,  发布年份 2014
【 摘 要 】

Background

Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important differential diagnostic, prognostic and therapeutic implications. So-called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection rates.

Objective

To compare directly the AQP4-IgG detection rates of the currently most widely used commercial CBA, which employs cells transfected with a full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed CBA from the same manufacturer employing cells transfected with human M23-AQP4-DNA.

Methods

Results from 368 serum samples that had been referred for routine AQP4-IgG determination and had been tested in parallel in the two assays were compared.

Results

Seventy-seven out of 368 samples (20.9%) were positive for NMO-IgG/AQP4-Ab in at least one assay. Of these, 73 (94.8%) were positive in both assays. A single sample (1.3%) was exclusively positive in the novel assay; three samples (3.9%) were unequivocally positive only in the ‘classic’ assay due to high background intensity in the novel assay. Both median fluorescence intensity and background intensity were higher in the new assay.

Conclusions

This large study did not reveal significant differences in AQP4-IgG detection rates between the ‘classic’ CBA and a new M23-DNA-based CBA. Importantly, our results largely re-affirm the validity of previous studies that had used the ‘classic’ AQP4-CBA to establish NMO-IgG/AQP4-Ab seropositivity rates in NMO and in a variety of NMO spectrum disorders.

【 授权许可】

   
2014 Jarius et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, Hellwig K, Hemmer B, Linker RA, Lauda F, Mayer CA, Tumani H, Melms A, Trebst C, Stangel M, Marziniak M, Hoffmann F, Schippling S, Faiss JH, Neuhaus O, Ettrich B, Zentner C, Guthke K, Hofstadt-van Oy U, Reuss R, Pellkofer H, et al.: Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 2012, 9:14.
  • [2]Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T: Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2013, 261:1-16.
  • [3]Wildemann B, Jarius S, Paul F: Neuromyelitis optica. Nervenarzt 2013, 84:436-441.
  • [4]Jarius S, Wildemann B: The history of neuromyelitis optica. J Neuroinflammation 2013, 10:8.
  • [5]Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG: A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004, 364:2106-2112.
  • [6]Jarius S, Franciotta D, Bergamaschi R, Wright H, Littleton E, Palace J, Hohlfeld R, Vincent A: NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 2007, 68:1076-1077.
  • [7]Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR: IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005, 202:473-477.
  • [8]Paul F, Jarius S, Aktas O, Bluthner M, Bauer O, Appelhans H, Franciotta D, Bergamaschi R, Littleton E, Palace J, Seelig HP, Hohlfeld R, Vincent A, Zipp F: Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med 2007, 4:e133.
  • [9]Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld R, Vincent A, Wildemann B: Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol 2008, 4:202-214.
  • [10]Jarius S, Wildemann B: AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 2010, 6:383-392.
  • [11]Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W: Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008, 131:3072-3080.
  • [12]Levy M, Wildemann B, Jarius S, Orellano B, Sasidharan S, Weber MS, Stuve O: Immunopathogenesis of neuromyelitis optica. Adv Immunol 2014, 121:213-242.
  • [13]Jarius S, Wildemann B, Paul F: Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol 2014, 176:149-164.
  • [14]Wildemann B, Jarius S: The expanding range of autoimmune disorders of the nervous system. Lancet Neurol 2013, 12:22-24.
  • [15]Wildemann B, Bien CG: Immune-mediated encephalomyelitis. Nervenarzt 2013, 84:435.
  • [16]Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, Cowell JK, Dalmau J: Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010, 9:776-785.
  • [17]Reindl M, Di Pauli F, Rostasy K, Berger T: The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013, 9:455-461.
  • [18]Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen MB, Grisold W, Kimura A, Ohta K, Iizuka T, Guzman M, Graus F, Moss SJ, Balice-Gordon R, Dalmau J: Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010, 9:67-76.
  • [19]Jarius S, Wandinger KP, Horn S, Heuer H, Wildemann B: A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: immunological characterization. J Neuroinflammation 2010, 7:21.
  • [20]Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C, Lang B, Vincent A: Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 2010, 133:2734-2748.
  • [21]Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, Mata S, Kremens D, Vitaliani R, Geschwind MD, Bataller L, Kalb RG, Davis R, Graus F, Lynch DR, Balice-Gordon R, Dalmau J: AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009, 65:424-434.
  • [22]Jarius S, Frederikson J, Waters P, Paul F, Akman-Demir G, Marignier R, Franciotta D, Ruprecht K, Kuenz B, Rommer P, Kristoferitsch W, Wildemann B, Vincent A: Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis. J Neurol Sci 2010, 298:158-162.
  • [23]Matiello M, Lennon VA, Jacob A, Pittock SJ, Lucchinetti CF, Wingerchuk DM, Weinshenker BG: NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology 2008, 70:2197-2200.
  • [24]Petzold A, Pittock S, Lennon V, Maggiore C, Weinshenker BG, Plant GT: Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis. J Neurol Neurosurg Psychiatry 2010, 81:109-111.
  • [25]Akman-Demir G, Tuzun E, Waters P, Icoz S, Kurtuncu M, Jarius S, Yapici Z, Mutlu M, Yesilot N, Vincent A, Eraksoy M: Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients. J Neurol 2011, 258:464-470.
  • [26]Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, Wandinger KP: Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 2010, 291:52-56.
  • [27]Jarius S, Franciotta D, Paul F, Bergamaschi R, Rommer PS, Ruprecht K, Ringelstein M, Aktas O, Kristoferitsch W, Wildemann B: Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity, and direct comparison with immunohistochemistry. J Neurol Sci 2012, 320:32-37.
  • [28]Jarius S, Wildemann B: Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol 2013, 23:661-683.
  • [29]Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J, Maxwell S, Beeson D, Vincent A: Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008, 65:913-919.
  • [30]Waters P, Pittock SJ, Bennett JL, Jarius S, Weinshenker BG, Wingerchuk DM: Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol 2014. doi:10.1111/cen3.12107
  • [31]Kim W, Lee JE, Li XF, Kim SH, Han BG, Lee BI, Kim JK, Choi K, Kim HJ: Quantitative measurement of anti-aquaporin-4 antibodies by enzyme-linked immunosorbent assay using purified recombinant human aquaporin-4. Mult Scler 2012, 18:578-586.
  • [32]Waters PJ, McKeon A, Leite MI, Rajasekharan S, Lennon VA, Villalobos A, Palace J, Mandrekar JN, Vincent A, Bar-Or A, Pittock SJ: Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology 2012, 78:665-671. discussion 669
  • [33]Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J, Sato S, Itoyama Y: Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007, 130:1235-1243.
  • [34]Nicchia GP, Mastrototaro M, Rossi A, Pisani F, Tortorella C, Ruggieri M, Lia A, Trojano M, Frigeri A, Svelto M: Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies. Glia 2009, 57:1363-1373.
  • [35]Crane JM, Lam C, Rossi A, Gupta T, Bennett JL, Verkman AS: Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays. J Biol Chem 2011, 286:16516-16524.
  • [36]Marnetto F, Granieri L, Sala A, Frau J, Patanella AK, Gilli F, Capobianco M, Wandinger KP, Bertolotto A: Validation of a multi-parametric immunofluorescence assay for the detection of anti-AQP4 antibodies in the diagnosis of neuromyelitis optica. Mult Scler 2009, 15:P154.
  • [37]Granieri L, Marnetto F, Valentino P, Frau J, Patanella AK, Nytrova P, Sola P, Capobianco M, Jarius S, Bertolotto A: Evaluation of a multiparametric immunofluorescence assay for standardization of neuromyelitis optica serology. PLoS ONE 2012, 7:e38896.
  • [38]Pisani F, Sparaneo A, Tortorella C, Ruggieri M, Trojano M, Mola MG, Nicchia GP, Frigeri A, Svelto M: Aquaporin-4 autoantibodies in Neuromyelitis Optica: AQP4 isoform-dependent sensitivity and specificity. PLoS ONE 2013, 8:e79185.
  • [39]Rossi A, Pisani F, Nicchia GP, Svelto M, Frigeri A: Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: implication in orthogonal array formation and neuromyelitis optica antibody interaction. J Biol Chem 2010, 285:4562-4569.
  • [40]Mader S, Lutterotti A, Di Pauli F, Kuenz B, Schanda K, Aboul-Enein F, Khalil M, Storch MK, Jarius S, Kristoferitsch W, Berger T, Reindl M: Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica. PLoS ONE 2010, 5:e10455.
  • [41]Jiao Y, Fryer JP, Lennon VA, Jenkins SM, Quek AM, Smith CY, McKeon A, Costanzi C, Iorio R, Weinshenker BG, Wingerchuk DM, Shuster EA, Lucchinetti CF, Pittock SJ: Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica. Neurology 2013, 81:1197-1204.
  • [42]Kalluri SR, Illes Z, Srivastava R, Cree B, Menge T, Bennett JL, Berthele A, Hemmer B: Quantification and functional characterization of antibodies to native aquaporin 4 in neuromyelitis optica. Arch Neurol 2010, 67:1201-1208.
  • [43]Iorio R, Fryer JP, Hinson SR, Fallier-Becker P, Wolburg H, Pittock SJ, Lennon VA: Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays. J Autoimmun 2013, 40:21-27.
  • [44]Crane JM, Bennett JL, Verkman AS: Live cell analysis of aquaporin-4 M1/M23 interactions and regulated orthogonal array assembly in glial cells. J Biol Chem 2009, 284:35850-35860.
  • [45]Jarius S, Jacobi C, De Seze J, Zephir H, Paul F, Franciotta D, Rommer P, Mader S, Kleiter I, Reindl M, Akman-Demir G, Seifert-Held T, Kristoferitsch W, Melms A, Wandinger KP, Wildemann B: Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler 2011, 17:1067-1073.
  • [46]Zavada J, Nytrova P, Wandinger KP, Jarius S, Svobodova R, Probst C, Peterova V, Tegzova D, Pavelka K, Vencovsky J: Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus. Rheumatol Int 2013, 33:259-263.
  • [47]Von Glehn F, Jarius S, Penalva De Oliveira AC, Brandao CO, Farias AS, Damasceno A, Casseb J, Moraes AS, Longhini AL, Wandinger KP, Damasceno BP, Wildemann B, Santos LM: Aquaporin-4 antibodies are not related to HTLV-1 associated myelopathy. PLoS ONE 2012, 7:e39372.
  • [48]Jarius S, Paul F, Franciotta D, De Seze J, Munch C, Salvetti M, Ruprecht K, Liebetrau M, Wandinger KP, Akman-Demir G, Melms A, Kristoferitsch W, Wildemann B: Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature. Mult Scler 2012, 18:1135-1143.
  • [49]Wandinger KP, Stangel M, Witte T, Venables P, Charles P, Jarius S, Wildemann B, Probst C, Iking-Konert C, Schneider M: Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic lupus erythematosus and primary Sjogren’s syndrome. Arthritis Rheum 2010, 62:1198-1200.
  • [50]Jarius S, Franciotta D, Paul F, Ruprecht K, Bergamaschi R, Rommer PS, Reuss R, Probst C, Kristoferitsch W, Wandinger KP, Wildemann B: Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. J Neuroinflammation 2010, 7:52.
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