International multicenter examination of MOG antibody assays

Markus Reindl; Kathrin Schanda; Mark Woodhall; Fiona Tea; Sudarshini Ramanathan; Jessica Sagen; James P Fryer; John Mills; Bianca Teegen; Swantje Mindorf; Nora Ritter; Ulrike Krummrei; Winfried Stöcker; Juliane Eggert; Eoin P Flanagan; Melanie Ramberger; Harald Hegen; Kevin Rostasy; Thomas Berger; Maria Isabel Leite; Jacqueline Palace; Sarosh R Irani; Russell C Dale; Christian Probst; Monika Probst; Fabienne Brilot; Sean J Pittock; Patrick Waters

doi:10.1212/NXI.0000000000000674

International multicenter examination of MOG antibody assays

Neurol Neuroimmunol Neuroinflamm. 2020 Feb 5;7(2):e674. doi: 10.1212/NXI.0000000000000674. Print 2020 Mar 5.

Authors

Markus Reindl¹, Kathrin Schanda², Mark Woodhall², Fiona Tea², Sudarshini Ramanathan², Jessica Sagen², James P Fryer², John Mills², Bianca Teegen², Swantje Mindorf², Nora Ritter², Ulrike Krummrei², Winfried Stöcker², Juliane Eggert², Eoin P Flanagan², Melanie Ramberger², Harald Hegen², Kevin Rostasy², Thomas Berger², Maria Isabel Leite², Jacqueline Palace², Sarosh R Irani², Russell C Dale², Christian Probst², Monika Probst², Fabienne Brilot¹, Sean J Pittock¹, Patrick Waters¹

Affiliations

¹ From the Clinical Department of Neurology (M. Reindl, K.S., M. Ramberger, H.H.), Medical University of Innsbruck, Innsbruck, Austria; Oxford Autoimmune Neurology Group (M.W., M. Ramberger, M.I.L., J.P., S.R.I., P.W.), Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom; Brain Autoimmunity Group (F.T., S.R., R.C.D., F.B.), Kids Neuroscience Centre at Kids Research at the Children's Hospital at Westmead, Brain and Mind Centre, University of Sydney, New South Wales, Australia; Department of Neurology (J.S., J.P.F., J.M., E.P.F., S.J.P.), Mayo Clinic, Rochester, MN; Euroimmun Medizinische Labordiagnostika AG (B.T., S.M., N.R., U.K., W.S., C.P.), Lübeck, Germany; Institute for Quality Assurance (ifQ) affiliated to Euroimmun (J.E., M.P.), Lübeck, Germany; Paediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; and Department of Neurology (T.B.), Medical University of Vienna, Austria. markus.reindl@i-med.ac.at fabienne.brilot@sydney.edu.au pittock.sean@mayo.edu paddy.waters@ndcn.ox.ac.uk.
² From the Clinical Department of Neurology (M. Reindl, K.S., M. Ramberger, H.H.), Medical University of Innsbruck, Innsbruck, Austria; Oxford Autoimmune Neurology Group (M.W., M. Ramberger, M.I.L., J.P., S.R.I., P.W.), Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom; Brain Autoimmunity Group (F.T., S.R., R.C.D., F.B.), Kids Neuroscience Centre at Kids Research at the Children's Hospital at Westmead, Brain and Mind Centre, University of Sydney, New South Wales, Australia; Department of Neurology (J.S., J.P.F., J.M., E.P.F., S.J.P.), Mayo Clinic, Rochester, MN; Euroimmun Medizinische Labordiagnostika AG (B.T., S.M., N.R., U.K., W.S., C.P.), Lübeck, Germany; Institute for Quality Assurance (ifQ) affiliated to Euroimmun (J.E., M.P.), Lübeck, Germany; Paediatric Neurology (K.R.), Witten/Herdecke University, Children's Hospital Datteln, Datteln, Germany; and Department of Neurology (T.B.), Medical University of Vienna, Austria.

Abstract

Objective: To compare the reproducibility of 11 antibody assays for immunoglobulin (Ig) G and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG and MOG-IgM) from 5 international centers.

Methods: The following samples were analyzed: MOG-IgG clearly positive sera (n = 39), MOG-IgG low positive sera (n = 39), borderline negative sera (n = 13), clearly negative sera (n = 40), and healthy blood donors (n = 30). As technical controls, 18 replicates (9 MOG-IgG positive and 9 negative) were included. All samples and controls were recoded, aliquoted, and distributed to the 5 testing centers, which performed the following antibody assays: 5 live and 1 fixed immunofluorescence cell-based assays (CBA-IF, 5 MOG-IgG, and 1 MOG-IgM), 3 live flow cytometry cell-based assays (CBA-FACS, all MOG-IgG), and 2 ELISAs (both MOG-IgG).

Results: We found excellent agreement (96%) between the live CBAs for MOG-IgG for samples previously identified as clearly positive or negative from 4 different national testing centers. The agreement was lower with fixed CBA-IF (90%), and the ELISA showed no concordance with CBAs for detection of human MOG-IgG. All CBAs showed excellent interassay reproducibility. The agreement of MOG-IgG CBAs for borderline negative (77%) and particularly low positive (33%) samples was less good. Finally, most samples from healthy blood donors (97%) were negative for MOG-IgG in all CBAs.

Conclusions: Live MOG-IgG CBAs showed excellent agreement for high positive and negative samples at 3 international testing centers. Low positive samples were more frequently discordant than in a similar comparison of aquaporin-4 antibody assays. Further research is needed to improve international standardization for clinical care.

Publication types

Comparative Study
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies / blood*
Biological Assay / standards*
Enzyme-Linked Immunosorbent Assay / standards*
Flow Cytometry / standards*
Fluorescent Antibody Technique / standards*
Humans
Immunoglobulin G / blood*
Immunoglobulin M / blood*
Multicenter Studies as Topic / standards*
Myelin-Oligodendrocyte Glycoprotein / immunology*
Reproducibility of Results

Substances

Autoantibodies
Immunoglobulin G
Immunoglobulin M
MOG protein, human
Myelin-Oligodendrocyte Glycoprotein

Abstract

Publication types

MeSH terms

Substances

Grants and funding