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      Comparison of live and fixed cell-based assay performance: implications for the diagnosis of MOGAD in a low-middle income country

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          Abstract

          Background

          Though considered optimal, live cell-based assay (LCBA) is often unavailable for the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) in resource-poor regions. This study was undertaken to determine the agreement between LCBA and the widely available fixed cell-based assay (FCBA), for recommending testing guidelines within our region.

          Method

          All consecutive patients in our registry with a MOGAD phenotype were tested. The results from a commercially available FCBA (Euroimmun, Germany) were compared with a validated “in-house” LCBA. Clinical and MRI data were available for correlation.

          Results

          Among the 257 patient samples tested, 118 (45.9%) were positive by FCBA titre ≥1: 10 and or LCBA titres ≥1: 160 titre and 139 samples were negative. There was robust agreement between the two assays (agreement 98.8%, Cohen’s kappa 0.98 [95% CI- 0.95-1.00], Spearman correlation 0.97 (p < 0.0001). Among five discordant samples, four had clinical and or MRI data which supported an alternate diagnosis. There was a modest correlation between assay titres, particularly for samples with titres ≥ 1:100 in FCBA (Spearman’s Rho 0.26, p 0.005). Thirty samples were positive by FCBA at < 1:100 titre and included 1:80 (20),1:40(7) and 1:10 (3) titres. Among them, 80% had clear positive titres when tested by LCBA.

          Conclusion

          The FCBA tested with serum dilutions of 1:10 was highly predictive of MOGAD in our study and compared well with our “in-house” LCBA. The current recommendations for testing at higher dilutions need to be re-examined in light of our findings. The results of our study should ideally be replicated in a larger dataset but at the same time provide some guidance for the accurate diagnosis of MOGAD in resource-poor settings.

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          Most cited references23

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          Clinical presentation and prognosis in MOG-antibody disease: a UK study

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            Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria

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              Myelin oligodendrocyte glycoprotein antibodies in neurological disease

              Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                29 August 2023
                2023
                : 14
                : 1252650
                Affiliations
                [1] Center for Advanced Neurological Research, Nitte University , Mangalore, India
                Author notes

                Edited by: Edgar Carnero Contentti, Hospital Aleman, Argentina

                Reviewed by: Sara Mariotto, University of Verona, Italy; Tammy Smith, The University of Utah, United States

                Article
                10.3389/fimmu.2023.1252650
                10495565
                37705970
                7f6134b1-b851-4018-ad10-5d064d33c959
                Copyright © 2023 Pandit, D’Cunha, Malli and Sudhir

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 July 2023
                : 07 August 2023
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 23, Pages: 6, Words: 2609
                Funding
                This study was partly funded by the Indian council of medical research (ICMR)-No.5/4-5/Neuro/223/2020-NCD-1.
                Categories
                Immunology
                Original Research
                Custom metadata
                Multiple Sclerosis and Neuroimmunology

                Immunology
                mogad,international diagnostic criteria,live cell-based assay,fixed cellbased assay,assay performance

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