MOG cell-based assay detects non-MS patients with inflammatory neurologic disease
Objective: To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay. Methods: Consecutive sera (n 5 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG...
Main Authors: | , , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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Lippincott, Williams and Wilkins
2015
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author | Waters, P Woodhall, M O'Connor, K Reindl, M Lang, B Sato, D Juryńczyk, M Tackley, G Rocha, J Takahashi, T Misu, T Nakashima, I Palace, J Fujihara, K Leite, M Vincent, A |
author_facet | Waters, P Woodhall, M O'Connor, K Reindl, M Lang, B Sato, D Juryńczyk, M Tackley, G Rocha, J Takahashi, T Misu, T Nakashima, I Palace, J Fujihara, K Leite, M Vincent, A |
author_sort | Waters, P |
collection | OXFORD |
description | Objective: To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay. Methods: Consecutive sera (n 5 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG (FL-MOG) or the short-length form (SL-MOG). The Abs were initially detected by Alexa Fluor goat anti-human IgG (H 1 L) and subsequently by Alexa Fluor mouse antibodies to human IgG1. Results: When tested at 1:20 dilution, 40/1,109 sera were positive for AQP4-Abs, 21 for SLMOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab–positive sera was positive for SLMOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p 5 0.0069). Of equal concern, 48% (42/88) of sera from controls (patients with epilepsy) were positive by FL-MOG assay. However, using an IgG1-specific secondary antibody, only 65/1,109 (5.8%) sera were positive on FL-MOG, and AQP4-Ab– positive and control sera were negative. IgM reactivity accounted for the remaining anti-human IgG (H 1 L) positivity toward FL-MOG. The clinical diagnoses were obtained in 33 FL-MOG–positive patients, blinded to the antibody data. IgG1-Abs to FL-MOG were associated with optic neuritis (n 5 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n 5 4), and acute disseminated encephalomyelitis (n 5 1). All 7 patients with probable multiple sclerosis (MS) were MOG-IgG1 negative. Conclusions: The limited disease specificity of FL-MOG-Abs identified using Alexa Fluor goat antihuman IgG (H 1 L) is due in part to detection of IgM-Abs. Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases. Classification of evidence: This study provides Class II evidence that the presence of serum IgG1- MOG-Abs in AQP4-Ab–negative patients distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%–45%; specificity 100%, 95% CI 88%–100%). |
first_indexed | 2024-03-06T22:15:00Z |
format | Journal article |
id | oxford-uuid:5316210e-8a3e-41bf-bc34-440343c99927 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T22:15:00Z |
publishDate | 2015 |
publisher | Lippincott, Williams and Wilkins |
record_format | dspace |
spelling | oxford-uuid:5316210e-8a3e-41bf-bc34-440343c999272022-03-26T16:29:32ZMOG cell-based assay detects non-MS patients with inflammatory neurologic diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5316210e-8a3e-41bf-bc34-440343c99927EnglishSymplectic Elements at OxfordLippincott, Williams and Wilkins2015Waters, PWoodhall, MO'Connor, KReindl, MLang, BSato, DJuryńczyk, MTackley, GRocha, JTakahashi, TMisu, TNakashima, IPalace, JFujihara, KLeite, MVincent, AObjective: To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay. Methods: Consecutive sera (n 5 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG (FL-MOG) or the short-length form (SL-MOG). The Abs were initially detected by Alexa Fluor goat anti-human IgG (H 1 L) and subsequently by Alexa Fluor mouse antibodies to human IgG1. Results: When tested at 1:20 dilution, 40/1,109 sera were positive for AQP4-Abs, 21 for SLMOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab–positive sera was positive for SLMOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p 5 0.0069). Of equal concern, 48% (42/88) of sera from controls (patients with epilepsy) were positive by FL-MOG assay. However, using an IgG1-specific secondary antibody, only 65/1,109 (5.8%) sera were positive on FL-MOG, and AQP4-Ab– positive and control sera were negative. IgM reactivity accounted for the remaining anti-human IgG (H 1 L) positivity toward FL-MOG. The clinical diagnoses were obtained in 33 FL-MOG–positive patients, blinded to the antibody data. IgG1-Abs to FL-MOG were associated with optic neuritis (n 5 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n 5 4), and acute disseminated encephalomyelitis (n 5 1). All 7 patients with probable multiple sclerosis (MS) were MOG-IgG1 negative. Conclusions: The limited disease specificity of FL-MOG-Abs identified using Alexa Fluor goat antihuman IgG (H 1 L) is due in part to detection of IgM-Abs. Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases. Classification of evidence: This study provides Class II evidence that the presence of serum IgG1- MOG-Abs in AQP4-Ab–negative patients distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%–45%; specificity 100%, 95% CI 88%–100%). |
spellingShingle | Waters, P Woodhall, M O'Connor, K Reindl, M Lang, B Sato, D Juryńczyk, M Tackley, G Rocha, J Takahashi, T Misu, T Nakashima, I Palace, J Fujihara, K Leite, M Vincent, A MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title | MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title_full | MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title_fullStr | MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title_full_unstemmed | MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title_short | MOG cell-based assay detects non-MS patients with inflammatory neurologic disease |
title_sort | mog cell based assay detects non ms patients with inflammatory neurologic disease |
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