Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays

P. J. Waters, Andrew B McKeon, M. I. Leite, S. Rajasekharan, Vanda A Lennon, A. Villalobos, J. Palace, Jayawant Mandrekar, A. Vincent, A. Bar-Or, Sean J Pittock

Research output: Contribution to journalArticle

298 Citations (Scopus)

Abstract

Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). Methods: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77%; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis ofNMOspectrum disorders and prompt initiation of disease-appropriate therapies.

Original languageEnglish (US)
Pages (from-to)665-671
Number of pages7
JournalNeurology
Volume78
Issue number9
DOIs
StatePublished - Feb 28 2012

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Aquaporin 4
Neuromyelitis Optica
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Relapsing-Remitting Multiple Sclerosis
Sensitivity and Specificity
Demyelinating Diseases
Immunoprecipitation
Autoantibodies
Autoimmune Diseases
Fluorescent Antibody Technique
Early Diagnosis
Healthy Volunteers
Flow Cytometry
Fluorescence
Observation
Antigens
Cells
Serum

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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Serologic diagnosis of NMO : A multicenter comparison of aquaporin-4-IgG assays. / Waters, P. J.; McKeon, Andrew B; Leite, M. I.; Rajasekharan, S.; Lennon, Vanda A; Villalobos, A.; Palace, J.; Mandrekar, Jayawant; Vincent, A.; Bar-Or, A.; Pittock, Sean J.

In: Neurology, Vol. 78, No. 9, 28.02.2012, p. 665-671.

Research output: Contribution to journalArticle

Waters, PJ, McKeon, AB, Leite, MI, Rajasekharan, S, Lennon, VA, Villalobos, A, Palace, J, Mandrekar, J, Vincent, A, Bar-Or, A & Pittock, SJ 2012, 'Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays', Neurology, vol. 78, no. 9, pp. 665-671. https://doi.org/10.1212/WNL.0b013e318248dec1
Waters, P. J. ; McKeon, Andrew B ; Leite, M. I. ; Rajasekharan, S. ; Lennon, Vanda A ; Villalobos, A. ; Palace, J. ; Mandrekar, Jayawant ; Vincent, A. ; Bar-Or, A. ; Pittock, Sean J. / Serologic diagnosis of NMO : A multicenter comparison of aquaporin-4-IgG assays. In: Neurology. 2012 ; Vol. 78, No. 9. pp. 665-671.
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abstract = "Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). Methods: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77{\%}; 46 of 60) or visual observation (CBA, 73{\%}; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48{\%}-53{\%}). The CBA and ELISA commercial assays (100{\%} specific) yielded sensitivities of 68{\%} (41 of 60) and 60{\%} (36 of 60), respectively, and sensitivity of 72{\%} (43 of 60) when used in combination. Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis ofNMOspectrum disorders and prompt initiation of disease-appropriate therapies.",
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T2 - A multicenter comparison of aquaporin-4-IgG assays

AU - Waters, P. J.

AU - McKeon, Andrew B

AU - Leite, M. I.

AU - Rajasekharan, S.

AU - Lennon, Vanda A

AU - Villalobos, A.

AU - Palace, J.

AU - Mandrekar, Jayawant

AU - Vincent, A.

AU - Bar-Or, A.

AU - Pittock, Sean J

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N2 - Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). Methods: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77%; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis ofNMOspectrum disorders and prompt initiation of disease-appropriate therapies.

AB - Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). Methods: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77%; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis ofNMOspectrum disorders and prompt initiation of disease-appropriate therapies.

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