Effects of the Positive Threshold and Data Analysis on Human MOG Antibody Detection by Live Flow Cytometry

Charabati, Marc; Pilli, Deepti; Ramanathan, Sudarshini; Lopez, Joseph A; Merheb, Vera; Lee, Fiona X Z; Zou, Alicia; Liyanage, Ganesha; Bassett, Chelsea B.; Thomsen, Selina; Reddel, Stephen W.; Barnett, Michael; Brown, David A.; Dale, Russell C.; Brilot, Fabienne

doi:10.3389/fimmu.2020.00119

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…Recent multicenter comparison revealed live CBA as the gold standard to detect MOG-Ab. 27,28,41,42 IgG Fc and IgG1 secondary antibody are considered equally in regard to specificity and thus recommended to detect MOG-Ab. 23,43 The higher consistency was observed in our study between our laboratory and laboratory 2, which both use live-CBA.…”

Section: Discussionmentioning

confidence: 99%

Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Held¹,

Kalluri²,

Berthele³

et al. 2021

Multiple Sclerosis Journal - Experimental, Translational and Cl

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Background Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.

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Section: Discussionmentioning

confidence: 99%

Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Held¹,

Kalluri²,

Berthele³

et al. 2021

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…In our study, the rMFI analysis had a slightly higher agreement with CBA-IF than DMFI analysis. However, the study by Tea et al (2020) revealed that the ratio analysis also has the sensitivity reduced by high background binding (26). Therefore, in a few cases, we may need to perform combined analysis and review the flow-cytometry plots to increase the accuracy of the assay results.…”

Section: Discussionmentioning

confidence: 99%

Detection of MOG-IgG in Clinical Samples by Live Cell-Based Assays: Performance of Immunofluorescence Microscopy and Flow Cytometry

et al. 2021

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Human antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) from immunoglobulin-G subclasses (MOG-IgG) have been recently associated with a new subgroup of neurological autoimmune diseases with distinct clinical characteristics from multiple sclerosis and neuromyelitis optica spectrum disorders. The use of MOG-IgG as a biomarker is an essential tool to assist in the diagnosis and clinical prognosis. The cell-based assay (CBA) is a methodology that expresses high levels of natively folded human MOG protein in the cell membrane being the methodology most used for clinical MOG-IgG diagnosis. However, there is still no consensus about the best approach to perform CBA to improve the results. The CBA using flow cytometry (CBA-FC) is an automated technique with objective quantification, reducing the subject of human bias that occurred at CBA using immunofluorescence (CBA-IF). In this study, we compared the performance of CBA-IF and CBA-FC as an acquisition tool analysis. The sera of 104 patients diagnosed with inflammatory Central Nervous System diseases were tested in both CBA-IF and CBA-FC. We used the dilution of 1:128 for CBA-IF and three different dilutions (1:20, 1:100, and 1:640) for CBA-FC. The CBA-FC and CBA-IF results had 88.5% agreement between assays and the CBA-IF titers by endpoint-dilution correlated with the CBA-FC titers. The highest serum dilution resulted in an increased CBA-FC specificity, but there was a reduction in the CBA-FC sensitivity. Our study showed that CBA-FC can be used in clinical practice as a diagnostic technique for MOG-IgG. In addition, in some specific cases, the combination of both techniques could be used as a tool to discriminate unspecific binding and overcome single assay limitations.

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“…Recent validation studies have demonstrated lower concordance in MOG Ab testing when determining the presence of MOG Ab in patients with borderline and low MOG Ab titres tested across international centres 178 . Differences in assay methodologies, data analyses and cut‐offs for MOG Ab positivity largely account for these discrepancies 179,180 . Moreover, studies on the isoform of MOG have shown that C‐terminal truncation of the full‐length protein decreases binding of human MOG Ab 181 and is likely because of the effect of truncation on the second hydrophobic domain of MOG which has recently been revealed to be important in the bivalent binding of human MOG Ab 170 .…”

Section: Current Trends and Future Directionsmentioning

confidence: 99%

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody‐associated disease

et al. 2021

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Autoimmunity plays a significant role in the pathogenesis of demyelination. Multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are now recognised as separate disease entities under the amalgam of human central nervous system demyelinating disorders. While these disorders share inherent similarities, investigations into their distinct clinical presentations and lesion pathologies have aided in differential diagnoses and understanding of disease pathogenesis. An interplay of various genetic and environmental factors contributes to each disease, many of which implicate an autoimmune response. The pivotal role of the adaptive immune system has been highlighted by the diagnostic autoantibodies in NMOSD and MOGAD, and the presence of autoreactive lymphocytes in MS lesions. While a number of autoantigens have been proposed in MS, recent emphasis on the contribution of B cells has shed new light on the well-established understanding of T cell involvement in pathogenesis. This review aims to synthesise the clinical characteristics and pathological findings, discuss existing and emerging hypotheses regarding the aetiology of demyelination and evaluate recent pathogenicity studies involving T cells, B cells, and autoantibodies and their implications in human demyelination.

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Effects of the Positive Threshold and Data Analysis on Human MOG Antibody Detection by Live Flow Cytometry

Cited by 7 publications

References 42 publications

Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

Detection of MOG-IgG in Clinical Samples by Live Cell-Based Assays: Performance of Immunofluorescence Microscopy and Flow Cytometry

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody‐associated disease

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