title: MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.
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.
  
  
  METHODS
  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%).
authors.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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.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.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhall
authors.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.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.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.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.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.
authors.forename: Bethan
authors.initials: B
authors.lastname: Lang
authors.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.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Sato
authors.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.
authors.forename: Maciej
authors.initials: M
authors.lastname: Juryńczyk
authors.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.
authors.forename: George
authors.initials: G
authors.lastname: Tackley
authors.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.
authors.forename: Joao
authors.initials: J
authors.lastname: Rocha
authors.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.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.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.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.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.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.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.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
authors.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.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.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.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Leite
authors.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.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13992-7
references.pmid: 16172404
references.citation: Nat Med. 2007 Feb;13(2):211-7
references.pmid: 17237795
references.citation: J Exp Med. 2014 Jun 30;211(7):1465-83
references.pmid: 24935259
references.citation: Neurology. 2004 Jun 8;62(11):2092-4
references.pmid: 15184621
references.citation: Mult Scler. 2007 Jan;13(1):7-16
references.pmid: 17294606
references.citation: Neurosci Lett. 2001 Jul 13;307(2):131-3
references.pmid: 11427318
references.citation: Mol Immunol. 1997 Jan;34(1):33-8
references.pmid: 9182874
references.citation: J Neuroimmunol. 1991 Feb;31(2):91-6
references.pmid: 1991822
references.citation: Neurology. 2012 Feb 28;78(9):665-71; discussion 669
references.pmid: 22302543
references.citation: Arch Neurol. 2010 Sep;67(9):1102-8
references.pmid: 20837855
references.citation: J Immunol. 2013 Oct 1;191(7):3594-604
references.pmid: 24014878
references.citation: Arch Neurol. 2012 Jun;69(6):752-6
references.pmid: 22371853
references.citation: JAMA Neurol. 2014 Mar;71(3):276-83
references.pmid: 24425068
references.citation: Ann Neurol. 2009 Dec;66(6):833-42
references.pmid: 20033986
references.citation: Mult Scler. 2013 Jul;19(8):1052-9
references.pmid: 23257621
references.citation: N Engl J Med. 2003 Jul 10;349(2):139-45
references.pmid: 12853586
references.citation: Mult Scler. 2015 Apr;21(5):656-9
references.pmid: 25257613
references.citation: Neurology. 2012 Sep 18;79(12):1273-7
references.pmid: 22914827
references.citation: Brain. 1999 Nov;122 ( Pt 11):2047-56
references.pmid: 10545390
references.citation: Clin Neurol Neurosurg. 2007 Jan;109(1):23-6
references.pmid: 16750597
references.citation: Neurology. 2011 Aug 9;77(6):580-8
references.pmid: 21795651
references.citation: Arch Neurol. 1999 Mar;56(3):311-5
references.pmid: 10190821
references.citation: Neurol Neuroimmunol Neuroinflamm. 2014 May 22;1(1):e12
references.pmid: 25340056
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2280-5
references.pmid: 16461459
references.citation: N Engl J Med. 2007 Jan 25;356(4):426-8
references.pmid: 17251547
references.citation: Neurol Neuroimmunol Neuroinflamm. 2014 Oct 29;1(4):e40
references.pmid: 25364774
references.citation: J Immunol. 2009 Sep 15;183(6):4067-76
references.pmid: 19687098
references.citation: Neurology. 2004 Dec 28;63(12):2381-3
references.pmid: 15623705
references.citation: J Neuroimmunol. 2008 May 30;196(1-2):35-40
references.pmid: 18406472
references.citation: J Neuroinflammation. 2011 Dec 28;8:184
references.pmid: 22204662
references.citation: Neurology. 2014 Feb 11;82(6):474-81
references.pmid: 24415568
references.citation: Mult Scler. 2005 Aug;11(4):492-4
references.pmid: 16042235
references.citation: N Engl J Med. 2007 Jan 25;356(4):371-8
references.pmid: 17251533
references.citation: J Neuroophthalmol. 2012 Jun;32(2):107-10
references.pmid: 22157536
references.citation: Neurology. 2008 Oct 7;71(15):1142-6
references.pmid: 18753473
references.citation: Nat Rev Neurol. 2013 Aug;9(8):455-61
references.pmid: 23797245
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19057-62
references.pmid: 17142321
references.citation: J Mol Med (Berl). 1997 Feb;75(2):77-88
references.pmid: 9083925
references.citation: Mult Scler. 2001 Oct;7(5):285-9
references.pmid: 11724443
references.citation: J Neurol Sci. 2003 Jul 15;211(1-2):67-73
references.pmid: 12767500
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8207-12
references.pmid: 12060766