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MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.

Waters P, Woodhall M, O'Connor KC, Reindl M, Lang B, Sato DK, Juryńczyk M, Tackley G, Rocha J, Takahashi T, Misu T, Nakashima I, Palace J, Fujihara K, Leite MI, Vincent A - Neurol Neuroimmunol Neuroinflamm (2015)

Bottom Line: IgG1-Abs to FL-MOG were associated with optic neuritis (n = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 1).Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases.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%).

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Neurosciences (P.W., M.W., B.L., M.J., G.T., J.R., J.P., M.I.L., A.V.), John Radcliffe Hospital, Oxford, UK; Department of Neurology (K.C.O.), Yale School of Medicine, New Haven, CT; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Innsbruck, Austria; Department of Neurology (D.K.S., I.N.) and Department of Multiple Sclerosis Therapeutics (T.M., K.F.) Tohoku University School of Medicine, Sendai, Japan; and Department of Neurology (T.T.), Yonezawa National Hospital, Yonezawa, Japan.

ABSTRACT

Objective: To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay.

Methods: Consecutive sera (n = 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 + 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 SL-MOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab-positive sera was positive for SL-MOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p = 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 + 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 = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 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 anti-human IgG (H + 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%).

No MeSH data available.


Related in: MedlinePlus

Confirmatory cohorts to assess MOG-IgG1 assay(A) All 81 aquaporin-4 (AQP4)- seropositive patients (blue) from the Oxford National neuromyelitis optica (NMO) service were negative for IgG1 antibodies to myelin oligodendrocyte glycoprotein (MOG); however, 23 AQP4-seronegative patients were identified as MOG-IgG1 seropositive (red). Of the 58 patients with NMO, 37 (63.4%) were AQP4 seropositive, 8 (13.8%) were MOG-IgG1 seropositive, and 13 (22%) were double seronegative. (B) A second cohort from Japan was screened blinded to clinical information. None of the 49 AQP4-seropositive patients (blue) or 27 patients with multiple sclerosis (MS) were positive for MOG antibodies, but 6/25 patients with acute disseminated encephalomyelitis (ADEM), transverse myelitis (TM), optic neuritis (ON), or AQP4-seronegative NMO were MOG antibody positive (red). CBA = cell-based assay.
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Figure 4: Confirmatory cohorts to assess MOG-IgG1 assay(A) All 81 aquaporin-4 (AQP4)- seropositive patients (blue) from the Oxford National neuromyelitis optica (NMO) service were negative for IgG1 antibodies to myelin oligodendrocyte glycoprotein (MOG); however, 23 AQP4-seronegative patients were identified as MOG-IgG1 seropositive (red). Of the 58 patients with NMO, 37 (63.4%) were AQP4 seropositive, 8 (13.8%) were MOG-IgG1 seropositive, and 13 (22%) were double seronegative. (B) A second cohort from Japan was screened blinded to clinical information. None of the 49 AQP4-seropositive patients (blue) or 27 patients with multiple sclerosis (MS) were positive for MOG antibodies, but 6/25 patients with acute disseminated encephalomyelitis (ADEM), transverse myelitis (TM), optic neuritis (ON), or AQP4-seronegative NMO were MOG antibody positive (red). CBA = cell-based assay.

Mentions: AQP4-seropositive NMOSD patients (37 NMO, 11 TM, 33 ON) seen by the Oxford NMO service were negative for MOG-IgG1-Abs; however, 23 AQP4-seronegative patients (8 NMO, 1 TM, 9 ON, 1 ON + TM, 4 ADEM) were MOG-IgG1 positive (figure 4A, table 2). Thirteen patients with NMO were double seronegative. Hence, of the 58 patients seen in Oxford that fulfill the 2006 Wingerchuk criteria for NMO, 37 (63.8%) are AQP4 seropositive, 8 (13.8%) MOG-IgG1 positive, and 13 (22.4%) double seronegative.


MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.

Waters P, Woodhall M, O'Connor KC, Reindl M, Lang B, Sato DK, Juryńczyk M, Tackley G, Rocha J, Takahashi T, Misu T, Nakashima I, Palace J, Fujihara K, Leite MI, Vincent A - Neurol Neuroimmunol Neuroinflamm (2015)

Confirmatory cohorts to assess MOG-IgG1 assay(A) All 81 aquaporin-4 (AQP4)- seropositive patients (blue) from the Oxford National neuromyelitis optica (NMO) service were negative for IgG1 antibodies to myelin oligodendrocyte glycoprotein (MOG); however, 23 AQP4-seronegative patients were identified as MOG-IgG1 seropositive (red). Of the 58 patients with NMO, 37 (63.4%) were AQP4 seropositive, 8 (13.8%) were MOG-IgG1 seropositive, and 13 (22%) were double seronegative. (B) A second cohort from Japan was screened blinded to clinical information. None of the 49 AQP4-seropositive patients (blue) or 27 patients with multiple sclerosis (MS) were positive for MOG antibodies, but 6/25 patients with acute disseminated encephalomyelitis (ADEM), transverse myelitis (TM), optic neuritis (ON), or AQP4-seronegative NMO were MOG antibody positive (red). CBA = cell-based assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4370386&req=5

Figure 4: Confirmatory cohorts to assess MOG-IgG1 assay(A) All 81 aquaporin-4 (AQP4)- seropositive patients (blue) from the Oxford National neuromyelitis optica (NMO) service were negative for IgG1 antibodies to myelin oligodendrocyte glycoprotein (MOG); however, 23 AQP4-seronegative patients were identified as MOG-IgG1 seropositive (red). Of the 58 patients with NMO, 37 (63.4%) were AQP4 seropositive, 8 (13.8%) were MOG-IgG1 seropositive, and 13 (22%) were double seronegative. (B) A second cohort from Japan was screened blinded to clinical information. None of the 49 AQP4-seropositive patients (blue) or 27 patients with multiple sclerosis (MS) were positive for MOG antibodies, but 6/25 patients with acute disseminated encephalomyelitis (ADEM), transverse myelitis (TM), optic neuritis (ON), or AQP4-seronegative NMO were MOG antibody positive (red). CBA = cell-based assay.
Mentions: AQP4-seropositive NMOSD patients (37 NMO, 11 TM, 33 ON) seen by the Oxford NMO service were negative for MOG-IgG1-Abs; however, 23 AQP4-seronegative patients (8 NMO, 1 TM, 9 ON, 1 ON + TM, 4 ADEM) were MOG-IgG1 positive (figure 4A, table 2). Thirteen patients with NMO were double seronegative. Hence, of the 58 patients seen in Oxford that fulfill the 2006 Wingerchuk criteria for NMO, 37 (63.8%) are AQP4 seropositive, 8 (13.8%) MOG-IgG1 positive, and 13 (22.4%) double seronegative.

Bottom Line: IgG1-Abs to FL-MOG were associated with optic neuritis (n = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 1).Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases.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%).

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Neurosciences (P.W., M.W., B.L., M.J., G.T., J.R., J.P., M.I.L., A.V.), John Radcliffe Hospital, Oxford, UK; Department of Neurology (K.C.O.), Yale School of Medicine, New Haven, CT; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Innsbruck, Austria; Department of Neurology (D.K.S., I.N.) and Department of Multiple Sclerosis Therapeutics (T.M., K.F.) Tohoku University School of Medicine, Sendai, Japan; and Department of Neurology (T.T.), Yonezawa National Hospital, Yonezawa, Japan.

ABSTRACT

Objective: To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay.

Methods: Consecutive sera (n = 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 + 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 SL-MOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab-positive sera was positive for SL-MOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p = 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 + 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 = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 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 anti-human IgG (H + 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%).

No MeSH data available.


Related in: MedlinePlus