Validation of a Flow Cytometry Live Cell-Based Assay to Detect Myelin Oligodendrocyte Glycoprotein Antibodies for Clinical Diagnostics.

Autoantibodies Flow Cytometry Humans Immunoglobulin G Myelin-Oligodendrocyte Glycoprotein Reproducibility of Results
MOG antibody demyelinating disorders diagnostic validation flow cytometry

Journal

The journal of applied laboratory medicine
ISSN: 2576-9456
Titre abrégé: J Appl Lab Med
Pays: England
ID NLM: 101693884

Informations de publication

Date de publication:
05 01 2022
Historique:
received: 31 05 2021
accepted: 29 07 2021
pubmed: 1 11 2021
medline: 29 1 2022
entrez: 31 10 2021
Statut: ppublish

Résumé

Myelin oligodendrocyte glycoprotein antibodies (MOG Ab) are essential in the diagnosis of MOG Ab-associated disease (MOGAD). Live cell-based assays (CBAs) are the gold standard for MOG Ab detection with improved sensitivity and specificity over fixed CBAs. A number of testing centers have used flow cytometry for its high throughput and quantitative utility. Presently, there is increasing demand to translate these research-based methods into an accredited routine diagnostic setting. A flow cytometry live CBA was used to detect MOG Ab in patients with demyelination. Serostatuses were compared between a research-based assay and a streamlined diagnostic assay. Inter-laboratory validation of the streamlined assay was performed in an accredited diagnostic laboratory. Further streamlining was performed by introducing a borderline serostatus range and reducing the number of controls used to determine the positivity threshold. High serostatus agreement (98%-100%) was observed between streamlined and research-based assays. Intra- and inter-assay imprecision was improved in the streamlined assay (mean intra- and inter-assay CV = 7.3% and 27.8%, respectively) compared to the research-based assay (mean intra- and inter-assay CV = 11.8% and 33.6%, respectively). Borderline positive and clear positive serostatuses were associated with confirmed phenotypes typical of MOGAD. Compared to using 24 controls, robust serostatus classification was observed when using 13 controls without compromising analytical performance (93%-98.5% agreement). Flow cytometry live CBAs show robust utility in determining MOG Ab serostatus. Streamlining and standardizing use of this assay for diagnostics would improve the accuracy and reliability of routine testing to aid diagnosis and treatment of patients with demyelination.

Sections du résumé

BACKGROUND
Myelin oligodendrocyte glycoprotein antibodies (MOG Ab) are essential in the diagnosis of MOG Ab-associated disease (MOGAD). Live cell-based assays (CBAs) are the gold standard for MOG Ab detection with improved sensitivity and specificity over fixed CBAs. A number of testing centers have used flow cytometry for its high throughput and quantitative utility. Presently, there is increasing demand to translate these research-based methods into an accredited routine diagnostic setting.
METHODS
A flow cytometry live CBA was used to detect MOG Ab in patients with demyelination. Serostatuses were compared between a research-based assay and a streamlined diagnostic assay. Inter-laboratory validation of the streamlined assay was performed in an accredited diagnostic laboratory. Further streamlining was performed by introducing a borderline serostatus range and reducing the number of controls used to determine the positivity threshold.
RESULTS
High serostatus agreement (98%-100%) was observed between streamlined and research-based assays. Intra- and inter-assay imprecision was improved in the streamlined assay (mean intra- and inter-assay CV = 7.3% and 27.8%, respectively) compared to the research-based assay (mean intra- and inter-assay CV = 11.8% and 33.6%, respectively). Borderline positive and clear positive serostatuses were associated with confirmed phenotypes typical of MOGAD. Compared to using 24 controls, robust serostatus classification was observed when using 13 controls without compromising analytical performance (93%-98.5% agreement).
CONCLUSIONS
Flow cytometry live CBAs show robust utility in determining MOG Ab serostatus. Streamlining and standardizing use of this assay for diagnostics would improve the accuracy and reliability of routine testing to aid diagnosis and treatment of patients with demyelination.

Identifiants

DOI: 10.1093/jalm/jfab101 PMID: 34718586
pubmed: 34718586
pii: 6414512
doi: 10.1093/jalm/jfab101
doi:

Substances chimiques

Autoantibodies 0
Immunoglobulin G 0
Myelin-Oligodendrocyte Glycoprotein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12-25

Informations de copyright

© American Association for Clinical Chemistry 2021.

Auteurs

Joseph A Lopez (JA)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Samuel D Houston (SD)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
School of Biomedical Engineering, The University of Sydney, Sydney, Australia.

Fiona Tea (F)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Vera Merheb (V)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.

Fiona X Z Lee (FXZ)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.

Sandy Smith (S)

New South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.

David McDonald (D)

New South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.

Alicia Zou (A)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Ganesha Liyanage (G)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Deepti Pilli (D)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Martina Denkova (M)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Jeannette Lechner-Scott (J)

Hunter Medical Research Institute, Faculty of Medicine and Public Health, The University of Newcastle, Department of Neurology, John Hunter Hospital, Newcastle, Australia.

Anneke van der Walt (A)

Department of Neurosciences, Central Clinical School, Monash University, Melbourne, Australia.

Michael H Barnett (MH)

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Stephen W Reddel (SW)

Brain and Mind Centre, The University of Sydney, Sydney, Australia.
Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia.

Simon Broadley (S)

Menzies Health Institute Queensland, Gold Coast Campus, Griffith University Southport, Australia.
Department of Neurology, Gold Coast University Hospital, Southport, Australia.

Sudarshini Ramanathan (S)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia.
Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Russell C Dale (RC)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Brain and Mind Centre, The University of Sydney, Sydney, Australia.

David A Brown (DA)

New South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.
Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Westmead Institute for Medical Research, Sydney, Australia.

Fabienne Brilot (F)

Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, Australia.
Specialty of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Brain and Mind Centre, The University of Sydney, Sydney, Australia.
ORCID: 0000-0002-7025-2276

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Validation of a Flow Cytometry Live Cell-Based...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytophotométrie › Cytométrie en flux › Validation of a Flow Cytometry Live Cell-Based...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Validation of a Flow Cytometry Live Cell-Based...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Validation of a Flow Cytometry Live Cell-Based...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Autoantigènes › Glycoprotéine MOG › Validation of a Flow Cytometry Live Cell-Based...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Reproductibilité des résultats › Validation of a Flow Cytometry Live Cell-Based...