TY - JOUR
T1 - MOG cell-based assay detects non-MS patients with inflammatory neurologic disease
AU - Waters, Patrick
AU - Woodhall, Mark
AU - O'Connor, Kevin C.
AU - Reindl, Markus
AU - Lang, Bethan
AU - Sato, Douglas K.
AU - Jurynczyk, MacIej
AU - Tackley, George
AU - Rocha, Joao
AU - Takahashi, Toshiyuki
AU - Misu, Tatsuro
AU - Nakashima, Ichiro
AU - Palace, Jacqueline
AU - Fujihara, Kazuo
AU - Isabel Leite, M.
AU - Vincent, Angela
N1 - Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2015/6
Y1 - 2015/6
N2 - 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%).
AB - 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%).
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U2 - 10.1212/NXI.0000000000000089
DO - 10.1212/NXI.0000000000000089
M3 - Article
AN - SCOPUS:84952308004
SN - 2332-7812
VL - 2
SP - e89
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 3
ER -
