MOG cell-based assay detects non-MS patients with inflammatory neurologic disease
Patrick Waters,M Woodhall,Kevin C. O’Connor,Markus Reindl,Bethan Lang,Douglas Kazutoshi Sato,Maciej Juryńczyk,George Tackley,J. Rocha,Toshiyuki Takahashi,T. Misu,Ichiro Nakashima,Jacqueline Palace,Kazuo Fujihara,Maria Isabel Leite,Angela Vincent +15 more
TLDR
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%).Abstract:
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%). Neurol Neuroimmunol Neuroinflamm 2015;2:e89; doi: 10.1212/ NXI.0000000000000089read more
Citations
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Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria
Alan J. Thompson,Brenda Banwell,Frederik Barkhof,Frederik Barkhof,William M. Carroll,Timothy Coetzee,Giancarlo Comi,Jorge Correale,Franz Fazekas,Massimo Filippi,Mark S. Freedman,Kazuo Fujihara,Steven L. Galetta,Hans-Peter Hartung,Ludwig Kappos,Fred D. Lublin,Ruth Ann Marrie,Aaron E. Miller,David Miller,Xavier Montalban,Xavier Montalban,Ellen M. Mowry,Per Soelberg Sørensen,Mar Tintoré,Anthony Traboulsee,Maria Trojano,Bernard M. J. Uitdehaag,Sandra Vukusic,Sandra Vukusic,Emmanuelle Waubant,Brian G. Weinshenker,Stephen C. Reingold,Jeffrey A. Cohen +32 more
TL;DR: The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation.
Journal ArticleDOI
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome
Sven Jarius,Klemens Ruprecht,Ingo Kleiter,Nadja Borisow,Nasrin Asgari,Kalliopi Pitarokoili,Florence Pache,Oliver Stich,Lena-Alexandra Beume,Martin W. Hümmert,Marius Ringelstein,Corinna Trebst,Alexander Winkelmann,Alexander Schwarz,Mathias Buttmann,Hanna Zimmermann,Joseph Kuchling,Diego Franciotta,Marco Capobianco,Eberhard Siebert,Carsten Lukas,Mirjam Korporal-Kuhnke,Jürgen Haas,Kai Fechner,Alexander U. Brandt,Kathrin Schanda,Orhan Aktas,Friedemann Paul,Markus Reindl,Brigitte Wildemann +29 more
TL;DR: The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal.
Journal ArticleDOI
MOG encephalomyelitis: International recommendations on diagnosis and antibody testing
Sven Jarius,Friedemann Paul,Friedemann Paul,Orhan Aktas,Nasrin Asgari,Russell C. Dale,J. de Seze,Diego Franciotta,Kazuo Fujihara,Anu Jacob,Ho Jin Kim,Ingo Kleiter,T. Kümpfel,Michael J. Levy,Jacqueline Palace,Klemens Ruprecht,Albert Saiz,Corinna Trebst,Brian G. Weinshenker,Brigitte Wildemann +19 more
TL;DR: In this article, the authors proposed indications for MOG-IgG testing based on expert consensus, and gave a list of conditions atypical for MG-EM (red flags) that should prompt physicians to challenge a positive MOG IgG test result, and provided recommendations regarding assay methodology, specimen sampling and data interpretation.
Journal ArticleDOI
Clinical presentation and prognosis in MOG-antibody disease: a UK study.
Maciej Juryńczyk,Silvia Messina,Mark Woodhall,Naheed Raza,Rosie Everett,Adriana Roca-Fernandez,George Tackley,Shahd Hamid,Angela Sheard,Gavin L Reynolds,Saleel Chandratre,Cheryl Hemingway,Anu Jacob,Angela Vincent,M. Isabel Leite,Patrick Waters,Jacqueline Palace +16 more
TL;DR: MOG-antibody disease has a moderate relapse risk, which might be mitigated by medium term immunosuppression at onset, and permanent disability occurs in about half of patients and more often involves sphincter and erectile functions than vision or mobility.
MOG-Enzephalomyelitis: Internationale Empfehlungen zu Diagnose und Antikörpertestung [MOG encephalomyelitis: international recommendations on diagnosis and antibody testing]
Sven Jarius,Friedemann Paul,Orhan Aktas,Nasrin Asgari,Russell C. Dale,J. de Seze,Diego Franciotta,Kazuo Fujihara,Aude Jacob,Ho Jin Kim,I. Kleiter,T. Kümpfel,Michael J. Levy,Jacqueline Palace,Klemens Ruprecht,Albert Saiz,C. Trebst,Brian G. Weinshenker,B. Wildemann +18 more
TL;DR: Indications for MOG-IgG testing based on expert consensus are proposed and a list of conditions atypical for Mog-EM (“red flags”) are given that should prompt physicians to challenge a positive Mogenogenetically distinct test result.
References
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Journal ArticleDOI
Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders
Douglas Kazutoshi Sato,Dagoberto Callegaro,Marco Aurélio Lana-Peixoto,Patrick Waters,Frederico Jorge,Toshiyuki Takahashi,Ichiro Nakashima,Samira Luisa Apostolos-Pereira,Natalia Talim,Renata Simm,Angelina Maria Martins Lino,Tatsuro Misu,Maria Isabel Leite,Masashi Aoki,Kazuo Fujihara +14 more
TL;DR: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.
Journal ArticleDOI
Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event
Thomas Berger,Paul Rubner,Franz Schautzer,R Egg,Hanno Ulmer,Irmgard Mayringer,Erika Dilitz,Florian Deisenhammer,Markus Reindl +8 more
TL;DR: Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis.
Journal ArticleDOI
Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study.
J Kitley,Patrick Waters,Mark Woodhall,Maria Isabel Leite,Andrew G. Murchison,Jithin George,Wilhelm Küker,S Chandratre,Angela Vincent,Jacqueline Palace +9 more
TL;DR: Patients with MOG-Abs can fulfill the diagnostic criteria for NMO, but there are differences when compared with those with AQP4-Abs, which include a higher proportion of males, younger age, and greater likelihood of involvement of the conus and deep gray matter structures on imaging.
Journal ArticleDOI
Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays
Patrick Waters,Andrew McKeon,Maria Isabel Leite,Sathyanath Rajasekharan,Vanda A. Lennon,Ada Villalobos,Jacqueline Palace,Jay Mandrekar,Angela Vincent,Amit Bar-Or,Sean J. Pittock +10 more
TL;DR: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis of N MO spectrum disorders and prompt initiation of disease-appropriate therapies.
Journal ArticleDOI
Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype
J Kitley,M Woodhall,Patrick Waters,Maria Isabel Leite,E Devenney,J Craig,Jacqueline Palace,Angela Vincent +7 more
TL;DR: 4 patients with an NMO/NMOSD phenotype who had antibodies to MOG appear to have more favorable clinical outcomes than those with typical AQP4 antibody–mediated disease, and MOG antibody titers fell in all 4 patients.
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