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Poster Session 1 Abstracts Multiple Sclerosis Journal 2018; 24: (S2) 121–327 Poster Session 1 Diagnosis and differential diagnosis very poor and our results indicate that ELISA is not useful for the detection of human MOG-ab. However, phase I only focused on clearly positive and negative samples, and we are therefore cur- rently performing phase II using 100 additional samples (border- P330 line and lower positive, healthy controls, and replicates from An international multicentre validation experiment for phase I) to compare the sensitivity and specificity of assays. We MOG antibodies plan to perform a phase III to examine MOG-ab assays in routine M. Reindl1, K. Schanda1, M. Woodhall2, F. Tea3, S. diagnostic centres world-wide and are particularly interested in Ramanathan3, B. Teegen3, J. Sagen4, J. Fryer4, J. Mills4, centres that can contribute sera to the study. S. Mindorf5, N. Ritter5, U. Krummrei5, W. Stöcker5, J. Conclusions: Large multicentre validation studies of antibody Eggert6, K. Rostasy7, T. Berger1, S.R. Irani2, R. Dale3, C. assay are important to evaluate assay reproducibility between cen- Probst5, F. Brilot3, M. Probst6, S. Pittock4, P. Waters2 tres and to help define the clinical phenotype associated with 1Clinical Department of Neurology, Medical University of MOG-ab. Innsbruck, Innsbruck, Austria, 2Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, Disclosure University of Oxford, Oxford, United Kingdom, 3Brain Markus Reindl was supported by a research grant from the Autoimmunity Group and Kids Research at the Children’s Austrian Science Promotion Agency (FFG). The University Hospital at Westmead, Brain and Mind Centre, University of Hospital and Medical University of Innsbruck (Austria; M.R.) Sydney, Sydney, NSW, Australia, 4Department of Neurology, receives payments for antibody assays (MOG, AQP4, and other Mayo Clinic, Rochester, MN, United States, 5Euroimmun autoantibodies) and for MOG and AQP4 antibody validation Medizinische Labordiagnostika AG, 6Institute for Quality experiments organized by Euroimmun (Lübeck, Germany). Assurance affiliated to Euroimmun, Luebeck, 7Paediatric Kathrin Schanda was supported by a research grant from the Neurology, Witten/Herdecke University and Children’s Hospital Austrian Science Promotion Agency (FFG). Datteln, Datteln, Germany Mark Woodhall has no disclosure to report. Fiona Tea has no disclosure to report. Background: Antibodies to myelin-oligodendrocyte-glycoprotein Sudarshini Ramanathan has no disclosure to report. (MOG-ab) are associated with a broad spectrum of human CNS Bianca Teegen has received personal compensation from Labor demyelinating diseases including AQP4-ab-seronegative neuro- Dr. Stoecker as an employee. myelitis optica spectrum disorders and related clinical presenta- Jessica Sagen has no disclosure to report. tions such as isolated optic neuritis and myelitis, acute disseminated Jim Fryer has no disclosure to report. encephalomyelitis, but only rarely in multiple sclerosis. Although John Mills has no disclosure to report. numerous studies have used different immunoassays for MOG-ab, Swantje Mindorf has received personal compensation from there is no published blinded multi-centre validation experiments Euroimmun AG as an employee. comparing MOG-ab assays. The aim of our study was therefore to Nora Ritter has received personal compensation from Euroimmun compare the most frequently used assays for MOG-ab such as AG as an employee. immunofluorescence cell-based assays (IF-CBA), flow cytometry Ulrike Krummrei has received personal compensation from cell-based assays (FACS-CBA) and enzyme-linked immunosorb- Euroimmun AG as an employee. ent assay (ELISA). In phase one we compared 11 different Winfried Stöcker has received personal compensation from MOG-ab assays (in-house and commercial; IF-CBA, FACS-CBA Euroimmun AG as CEO. and ELISA) in a blinded fashion on 89 serum samples. Juliane Eggert has received personal compensation from Methods: The clinical laboratories (Innsbruck, Mayo, Oxford and Euroimmunas an employee of the Institute for Quality Assurance. Sydney) sent coded MOG-ab positive sera (n=39), MOG-ab nega- Kevin Rostasy has no disclosure to report. tive sera (n=40) and clinical documentation to the Institute for Thomas Berger: the University Hospital and Medical University Quality Assurance (IQA), Lübeck, Germany. Euroimmun AG of Innsbruck (Austria; T.B.) receives payments for antibody contributed 10 technical controls (humanized monoclonal anti- assays (MOG, AQP4, and other autoantibodies) and for MOG and bodies) which were also sent to the IQA. All samples and controls AQP4 antibody validation experiments organized by Euroimmun were re-coded, aliquoted and distributed to the five testing cen- (Lübeck, Germany). tres. Upon completion of the testing, the assay results from each Sarosh R Irani reports personal fees from MedImmune and has a centre was entered onto a web-based database. The data were then patent WO/2010/046716 entitled ‘Neurological Autoimmune unblinded, and analysed. Disorders’ with royalties paid. Results: We found a very good agreement between live IF-CBA Russell Dale was supported by research grants from the National and live FACS-CBA (kappa values > 0.9). There was a good Health and Medical Research Council (NHRMC), Multiple agreement between live CBA (IF or FACS) and fixed IF-CBA Sclerosis Research Australia (MSRA), and Trish Multiple Sclerosis (kappa values > 0.8). The agreement of ELISA and all CBA was Research Foundation. © 2018 SAGE Publications 10.1177/1352458518798582 122 Poster Session 1, 24(S2) Christian Probst has received personal compensation from Materials and methods: White matter T2/FLAIR hyperintensi- Euroimmun AG as an employee. ties of 84 migraine and 79 Clinically Isolated Syndrome (CIS) Fabienne Brilot was supported by research grants from the patients were volumetrically and topographically assessed by National Health and Medical Research Council (NHRMC), using manual segmentation technique and, subsequently, by gen- Multiple Sclerosis Research Australia (MSRA), and Trish erating Lesion Probability Maps (LPMs) and Voxel-Based Lesion Multiple Sclerosis Research Foundation. Symptom Mapping (VLSM). A logistic regression analysis based Monika Probst has received personal compensation from on lesion location was performed to evaluate the impact of 1 ver- Euroimmunas an employee of the Institute for Quality Assurance. sus 3 PVLs on the sensibility and specificity of the 2017 revisions Sean Pittock is a named inventor on filed patents that relate to func- and the 2016 MAGNIMS criteria. tional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; Results: CIS patients had a higher WMH number and volume in consulted for Alexion, Medimmune, Grifols and Euroimmun; and all the four locations analyzed. Interestingly, 10.7% of migraine received research support from Grifols, Medimmune, Alexion, patients showed infratentorial WMH, detectable through a careful Euroimmun, and AEA (Autoimmune Encephalitis Alliance). All evaluation of the posterior fossa on the T2-weighted images. compensation for consulting activities is paid directly to Mayo Logistic regression analysis showed that PVLs were the best fac- Clinic. tor separating CIS from migraine patients with a 85% decrease in Patrick Waters and the University of Oxford are named inventors the probability to be migraineur for each PVL more than one on patents for antibody assays and have received royalties. He has (OR=0.156, 95% CI=0.076, 0.319, p< 0.001). MAGNIMS criteria received honoraria or research funding from Biogen Idec, Mereo demonstrated the highest specificity in differentiating CIS from biopharma, Retrogenix and Euroimmun AG, and travel grants migraineur (100% vs 87%) against a predictable lower sensibility from the Guthy-Jackson Charitable Foundation. (63% vs 72%). Conclusions: PVLs play a key role in the differential diagnosis between migraine and CIS, particularly when they are ≥ 3. It P331 might be prudent for the clinician to consider a higher number of Migraine and clinically isolated syndrome: the role of PVLs, in order to avoid misdiagnosis. periventricular lesions. Disclosure 1 2 1 3 C. Lapucci , L.R. Saitta , G. Bommarito , M.P. Sormani , CL has received honoraria for travel expenses for attending meet- 1 1 1,4 M. Pardini , L. Bonzano , G.L. Mancardi , M. ings from Roche. 1,5 6 7 7 Inglese , C. Gasperini , N. De Stefano , A. Giorgio , L. LRS, GB, LB, AG, LR has nothing to disclose. 2,3 Roccatagliata MPS has received consulting fees from Biogen Idec, Merck 1 Department of Neuroscience, Rehabilitation, Ophthalmology, Serono, Teva, Genzyme, Roche, Novartis, GeNeuro and Medday. Genetics, Maternal and Child Health (DiNOGMI), University MP has received research support from Novartis and personal fees 2 3 of Genoa, Department of Neuroradiology, Department of from Teva and Merck. 4 Health Sciences (DISSAL), Department of Neurology, Ospedale GLM has received honoraria for lecturing, travel expenses for 5 Policlinico San Martino – IRCCS, Genoa, Italy, Department attending meetings, and financial support for research from Bayer of Neuroscience, Icahn School of Medicine, Mount Sinai, New Schering, Biogen Idec, Sanofi - Aventis, Merck Serono 6 York, NY, United States, Department of Neurosciences, S. Pharmaceuticals, Novartis, Genzyme and Teva. 7 Camillo-Forlanini Hospital, Rome, Department of Medicine, MI has received research grants from NIH, DOD, NMSS, FISM Surgery and Neuroscience, University of Siena, Siena, Italy and Teva Neuroscience.
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