Detection of MOG-IgG by cell-based assay: moving from discovery to clinical practice
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REVIEW ARTICLE
Detection of MOG-IgG by cell-based assay: moving from discovery to clinical practice Amanda Marchionatti 1,2 & Mark Woodhall 3 & Patrick Joseph Waters 3 & Douglas Kazutoshi Sato 1,2 Received: 18 May 2020 / Accepted: 12 October 2020 # Fondazione Società Italiana di Neurologia 2020
Abstract Myelin oligodendrocyte glycoprotein (MOG) is a unique CNS-specific mammalian protein that is expressed on the surface of compact myelin and oligodendrocyte cell bodies. MOG is an accessible target for autoantibodies, associated with immunemediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G antibodies (MOGIgG) helps to distinguish a subgroup of patients from multiple sclerosis and other CNS disorders, reducing the risk of clinical misdiagnosis. The development of the cell-based assays (CBA) improved the detection of clinically meaningful MOG-IgG binding to conformational MOG expressed in the cell membrane surface. In this review, we describe factors that impact on the results of CBA, such as MOG conformation, protein glycosylation, addition of fluorescent tags, serum dilution, secondary antibodies, and data interpretation. Keywords Myelin oligodendrocyte glycoprotein . Autoantibodies . CBA . Neuromyelitis optica spectrum disorder . Acute disseminating encephalomyelitis . Multiple sclerosis
Introduction Myelin oligodendrocyte glycoprotein (MOG) is a protein expressed on the surface of oligodendrocytes [1]. It is found throughout the central nervous system (CNS) in the brain, optic nerves, and spinal cord [2]. MOG has been identified as a target of immunoglobulin G antibodies (MOG-IgG), which has been associated with a subgroup of immunemediated CNS demyelinating diseases [3]. MOG antibodies were initially reported in association with multiple sclerosis (MS). However, these antibodies were detected by ELISA or western blot (WB). These tests also detected antibodies in healthy individuals and infectious control
* Douglas Kazutoshi Sato [email protected] 1
Neuroinflammation and Neuroimmunology Lab, Brain Institute of Rio Grande do Sul, Porto Alegre, Brazil
2
School of Medicine, Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
3
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK
populations suggesting a lack of clinical utility in detecting MOG antibodies using these methods [4]. Subsequently, the role of conformational sensitive MOG-IgG began to be investigated in other inflammatory demyelinating diseases of the CNS [5]. Even detecting antibodies against native protein demonstrates MOG-IgG in healthy individuals. However, when serum is diluted much more than in other tests, a clinical association appears. MOG-IgG was found in patients with any combination of optic neuritis, cortical encephalitis and/or myelitis, acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody negative neuromyelitis optica spectrum disorder (NMOSD
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