A multicenter comparison of MOG-IgG cell-based assays

Patrick J. Waters, Lars Komorowski, Mark Woodhall, Sabine Lederer, Masoud Majed, Jim Fryer, John Mills, Eoin Flanagan, Sarosh R. Irani, Amy C. Kunchok, Andrew McKeon, Sean J Pittock

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Abstract

OBJECTIVES: To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers. METHODS: Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from patients with multiple sclerosis (244), hypergammaglobulinemia (42), and other (17). Seropositivity was determined by visual observation on a fluorescence microscope (Euroimmun fixed CBA, Oxford live cell CBA) or flow cytometry (Mayo live cell fluorescence-activated cell sorting assay). RESULTS: Of 25 samples positive by any methodology, 21 were concordant on all 3 assays, 2 were positive at Oxford and Euroimmun, and 2 were positive only at Oxford. Euroimmun, Mayo, and Oxford results were as follows: clinical specificity 98.1%, 99.6%, and 100%; positive predictive values (PPVs) 82.1%, 95.5%, and 100%; and negative predictive values 79.0%, 78.8%, and 79.8%. Of 5 false-positives, 1 was positive at both Euroimmun and Mayo and 4 were positive at Euroimmun alone. CONCLUSIONS: Overall, a high degree of agreement was observed across 3 different MOG-IgG CBAs. Both live cell-based methodologies had superior PPVs to the fixed cell assays, indicating that positive results in these assays are more reliable indicators of MOG autoimmune spectrum disorders.

Original languageEnglish (US)
Pages (from-to)e1250-e1255
JournalNeurology
Volume92
Issue number11
DOIs
StatePublished - Mar 12 2019

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Gastrin-Secreting Cells
Immunoglobulin G
Flow Cytometry
Myelin-Oligodendrocyte Glycoprotein
Acute Disseminated Encephalomyelitis
Neuromyelitis Optica
Hypergammaglobulinemia
Optic Neuritis
Multiple Sclerosis
Fluorescence
Serum

ASJC Scopus subject areas

  • Clinical Neurology

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Waters, P. J., Komorowski, L., Woodhall, M., Lederer, S., Majed, M., Fryer, J., ... Pittock, S. J. (2019). A multicenter comparison of MOG-IgG cell-based assays. Neurology, 92(11), e1250-e1255. https://doi.org/10.1212/WNL.0000000000007096

A multicenter comparison of MOG-IgG cell-based assays. / Waters, Patrick J.; Komorowski, Lars; Woodhall, Mark; Lederer, Sabine; Majed, Masoud; Fryer, Jim; Mills, John; Flanagan, Eoin; Irani, Sarosh R.; Kunchok, Amy C.; McKeon, Andrew; Pittock, Sean J.

In: Neurology, Vol. 92, No. 11, 12.03.2019, p. e1250-e1255.

Research output: Contribution to journalArticle

Waters, PJ, Komorowski, L, Woodhall, M, Lederer, S, Majed, M, Fryer, J, Mills, J, Flanagan, E, Irani, SR, Kunchok, AC, McKeon, A & Pittock, SJ 2019, 'A multicenter comparison of MOG-IgG cell-based assays', Neurology, vol. 92, no. 11, pp. e1250-e1255. https://doi.org/10.1212/WNL.0000000000007096
Waters PJ, Komorowski L, Woodhall M, Lederer S, Majed M, Fryer J et al. A multicenter comparison of MOG-IgG cell-based assays. Neurology. 2019 Mar 12;92(11):e1250-e1255. https://doi.org/10.1212/WNL.0000000000007096
Waters, Patrick J. ; Komorowski, Lars ; Woodhall, Mark ; Lederer, Sabine ; Majed, Masoud ; Fryer, Jim ; Mills, John ; Flanagan, Eoin ; Irani, Sarosh R. ; Kunchok, Amy C. ; McKeon, Andrew ; Pittock, Sean J. / A multicenter comparison of MOG-IgG cell-based assays. In: Neurology. 2019 ; Vol. 92, No. 11. pp. e1250-e1255.
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abstract = "OBJECTIVES: To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers. METHODS: Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from patients with multiple sclerosis (244), hypergammaglobulinemia (42), and other (17). Seropositivity was determined by visual observation on a fluorescence microscope (Euroimmun fixed CBA, Oxford live cell CBA) or flow cytometry (Mayo live cell fluorescence-activated cell sorting assay). RESULTS: Of 25 samples positive by any methodology, 21 were concordant on all 3 assays, 2 were positive at Oxford and Euroimmun, and 2 were positive only at Oxford. Euroimmun, Mayo, and Oxford results were as follows: clinical specificity 98.1{\%}, 99.6{\%}, and 100{\%}; positive predictive values (PPVs) 82.1{\%}, 95.5{\%}, and 100{\%}; and negative predictive values 79.0{\%}, 78.8{\%}, and 79.8{\%}. Of 5 false-positives, 1 was positive at both Euroimmun and Mayo and 4 were positive at Euroimmun alone. CONCLUSIONS: Overall, a high degree of agreement was observed across 3 different MOG-IgG CBAs. Both live cell-based methodologies had superior PPVs to the fixed cell assays, indicating that positive results in these assays are more reliable indicators of MOG autoimmune spectrum disorders.",
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AU - Fryer, Jim

AU - Mills, John

AU - Flanagan, Eoin

AU - Irani, Sarosh R.

AU - Kunchok, Amy C.

AU - McKeon, Andrew

AU - Pittock, Sean J

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N2 - OBJECTIVES: To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers. METHODS: Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from patients with multiple sclerosis (244), hypergammaglobulinemia (42), and other (17). Seropositivity was determined by visual observation on a fluorescence microscope (Euroimmun fixed CBA, Oxford live cell CBA) or flow cytometry (Mayo live cell fluorescence-activated cell sorting assay). RESULTS: Of 25 samples positive by any methodology, 21 were concordant on all 3 assays, 2 were positive at Oxford and Euroimmun, and 2 were positive only at Oxford. Euroimmun, Mayo, and Oxford results were as follows: clinical specificity 98.1%, 99.6%, and 100%; positive predictive values (PPVs) 82.1%, 95.5%, and 100%; and negative predictive values 79.0%, 78.8%, and 79.8%. Of 5 false-positives, 1 was positive at both Euroimmun and Mayo and 4 were positive at Euroimmun alone. CONCLUSIONS: Overall, a high degree of agreement was observed across 3 different MOG-IgG CBAs. Both live cell-based methodologies had superior PPVs to the fixed cell assays, indicating that positive results in these assays are more reliable indicators of MOG autoimmune spectrum disorders.

AB - OBJECTIVES: To compares 3 different myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG) cell-based assays (CBAs) from 3 international centers. METHODS: Serum samples from 394 patients were as follows: acute disseminated encephalomyelitis (28), seronegative neuromyelitis optica (27), optic neuritis (21 single, 2 relapsing), and longitudinally extensive (10 single, 3 recurrent). The control samples were from patients with multiple sclerosis (244), hypergammaglobulinemia (42), and other (17). Seropositivity was determined by visual observation on a fluorescence microscope (Euroimmun fixed CBA, Oxford live cell CBA) or flow cytometry (Mayo live cell fluorescence-activated cell sorting assay). RESULTS: Of 25 samples positive by any methodology, 21 were concordant on all 3 assays, 2 were positive at Oxford and Euroimmun, and 2 were positive only at Oxford. Euroimmun, Mayo, and Oxford results were as follows: clinical specificity 98.1%, 99.6%, and 100%; positive predictive values (PPVs) 82.1%, 95.5%, and 100%; and negative predictive values 79.0%, 78.8%, and 79.8%. Of 5 false-positives, 1 was positive at both Euroimmun and Mayo and 4 were positive at Euroimmun alone. CONCLUSIONS: Overall, a high degree of agreement was observed across 3 different MOG-IgG CBAs. Both live cell-based methodologies had superior PPVs to the fixed cell assays, indicating that positive results in these assays are more reliable indicators of MOG autoimmune spectrum disorders.

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