Refining cell-based assay to detect MOG-IgG in patients with central nervous system inflammatory diseases.
Adolescent
Adult
Biological Assay
/ standards
Child
Child, Preschool
Demyelinating Autoimmune Diseases, CNS
/ blood
Female
Flow Cytometry
Fluorescent Antibody Technique
HEK293 Cells
Humans
Immunoglobulin G
/ blood
Inflammation
/ blood
Male
Middle Aged
Myelin-Oligodendrocyte Glycoprotein
/ immunology
Retrospective Studies
Sensitivity and Specificity
Young Adult
MOG-IgG
MOG-IgG assay
MOG-IgG associated diseases
cell-based assay
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
29
07
2019
revised:
03
01
2020
accepted:
07
01
2020
pubmed:
25
1
2020
medline:
26
1
2021
entrez:
25
1
2020
Statut:
ppublish
Résumé
Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. Here, we aim to validate a new in-house live cell-based assay (CBA) for screening MOG-IgG in patients with central nervous system inflammatory diseases. We generated a full length MOG transfected HEK293 stable cell line using pIRES2-eGFP vector. Sera from 355 patients with central nervous system inflammatory diseases and 25 healthy individuals were evaluated for MOG-IgG seropositivity using in-house cell-based immunofluorescence assay (CBA-IF). The specificity of IgG (H + L) and IgG1-Fc secondary antibodies as well as IgM binding were determined by cell-based flow cytometry (CBA-FACS). The optimal cut-offs for determining seropositivity in CBA-FACS were calculated and the concordance of CBA-IF score and CBA-FACS was studied. The results of our CBA-IF were compared with the Oxford CBA-IF. 11.5% (41/355) of patients were seropositive for MOG-IgG and had clinical phenotypes that were within the known clinical spectrum of MOG-IgG associated diseases. No typical multiple sclerosis patients, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder or healthy individuals were MOG-IgG seropositive. Using CBA-FACS, the anti-human IgG (H + L) was found to be comparable to IgG1-Fc antibody. No IgM binding was observed in all the samples tested. CBA-IF score and CBA-FACS yielded high correlation. The concordance of the NCC CBA-IF with the Oxford CBA-IF was 98%. We have developed MOG-IgG CBAs that have different characteristics and benefits but with high specificity and concordance. The complementary use of two methods and follow-up study with larger cohort will increase the clinical usefulness of MOG-IgG CBAs.
Sections du résumé
BACKGROUND
BACKGROUND
Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. Here, we aim to validate a new in-house live cell-based assay (CBA) for screening MOG-IgG in patients with central nervous system inflammatory diseases.
METHODS
METHODS
We generated a full length MOG transfected HEK293 stable cell line using pIRES2-eGFP vector. Sera from 355 patients with central nervous system inflammatory diseases and 25 healthy individuals were evaluated for MOG-IgG seropositivity using in-house cell-based immunofluorescence assay (CBA-IF). The specificity of IgG (H + L) and IgG1-Fc secondary antibodies as well as IgM binding were determined by cell-based flow cytometry (CBA-FACS). The optimal cut-offs for determining seropositivity in CBA-FACS were calculated and the concordance of CBA-IF score and CBA-FACS was studied. The results of our CBA-IF were compared with the Oxford CBA-IF.
RESULTS
RESULTS
11.5% (41/355) of patients were seropositive for MOG-IgG and had clinical phenotypes that were within the known clinical spectrum of MOG-IgG associated diseases. No typical multiple sclerosis patients, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder or healthy individuals were MOG-IgG seropositive. Using CBA-FACS, the anti-human IgG (H + L) was found to be comparable to IgG1-Fc antibody. No IgM binding was observed in all the samples tested. CBA-IF score and CBA-FACS yielded high correlation. The concordance of the NCC CBA-IF with the Oxford CBA-IF was 98%.
CONCLUSION
CONCLUSIONS
We have developed MOG-IgG CBAs that have different characteristics and benefits but with high specificity and concordance. The complementary use of two methods and follow-up study with larger cohort will increase the clinical usefulness of MOG-IgG CBAs.
Identifiants
pubmed: 31978673
pii: S2211-0348(20)30015-8
doi: 10.1016/j.msard.2020.101939
pii:
doi:
Substances chimiques
Immunoglobulin G
0
MOG protein, human
0
Myelin-Oligodendrocyte Glycoprotein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101939Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interests Kim YS, Hyun JW, Woodhall MR, Oh YM, Lee JE, Jung JY, Kim SY, Lee MY, Kim SH, Kim W and Choi K has nothing to declare. Irani SR and Waters P are co-applicants and receive royalties on patent application WO/2010/046,716 entitled 'Neurological Autoimmune Disorders'. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. SRI and PW are coinventors on ‘ADiagnostic Strategy to improve specificity of CASPR2 antibody detection.’ Kim HJ received a grant from the National Research Foundation of Korea; received research support Genzyme, Merck Serono, Teva-Handok, and UCB; received consultancy/speaker fees from Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; serves on a steering committee for MedImmune/VielaBio; is a co-editor for the Multiple Sclerosis Journal – Experimental, Translational, and Clinical, and an associated editor for the Journal of Clinical Neurology.