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Detection of MOG-IgG by cell-based assay: moving from discovery to clinical practice

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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 immune-mediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G antibodies (MOG-IgG) 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.

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Data availability

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Abbreviations

ADEM:

acute disseminated encephalomyelitis

AQP4:

aquaporin-4

CBA:

cell-based assay

CHO:

Chinese hamster ovary

CNS:

central nervous system

eGFP:

enhanced green fluorescent protein

ELISA:

enzyme-linked immunonosorbent assay

FACS:

fluorescence-activated cell sorting

FITC:

fluorescein isothiocyanate

FL-MOG:

full-length MOG

GFP:

green fluorescent protein

HEK293:

human embryonic kidney 293

IIF:

indirect immunofluorescence

IgG:

immunoglobulin G

IgM:

immunoglobulin M

LGI1:

leucine-rich glioma inactivated 1

MFI:

median fluorescent intensity

MHC:

major histocompatibility complex

MOG:

myelin oligodendrocyte glycoprotein

mRNA:

messenger ribonucleic acid

NMOSD:

neuromyelitis optica spectrum disorder

PEI:

polyethylenimine

RIA:

radioimmunoassay

SL-MOG:

short-length MOG

WB:

western blot

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Funding

This review is based on research supported by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior, Brasil (CAPES), Finance Code 001.

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All authors contributed to the manuscript preparation and wrote, read, and approved the submitted version.

Corresponding author

Correspondence to Douglas Kazutoshi Sato.

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Conflict of interest

The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

AM has received a scholarship from CAPES/Brazil.

MW has no disclosures.

PW and the University of Oxford hold patents and receive royalties for antibody assays. PW has received honoraria from Alexion and UBC and a research grant from Euroimmun AG.

DKS has received a scholarship from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; a Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 15K19472); research support from CNPq/Brazil (425331/2016-4), FAPERGS/MS/CNPq/SESRS (17/2551-0001391-3) PPSUS/Brazil, TEVA (research grant for EMOCEMP Investigator Initiated Study), and Euroimmun AG (Neuroimmunological Complications associated with Arboviruses); and speaker honoraria from Biogen, Novartis, Genzyme, TEVA, Merck Serono, Roche, and Bayer and has participated in advisory boards for Shire, Roche, TEVA, Merck Serono, and Quest/Athena Diagnostics.

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Marchionatti, A., Woodhall, M., Waters, P.J. et al. Detection of MOG-IgG by cell-based assay: moving from discovery to clinical practice. Neurol Sci 42, 73–80 (2021). https://doi.org/10.1007/s10072-020-04828-1

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