Comparative Analysis of T-Cell Responses to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in Inflammatory Demyelinating Central Nervous System Diseases

Hofer, Livia Sophie; Ramberger, Melanie; Gredler, Viktoria; Pescoller, Anna Sophie; Rostásy, Kevin; Sospedra, Mireia; Hegen, Harald; Berger, Thomas; Lutterotti, Andreas; Reindl, Markus

doi:10.3389/fimmu.2020.01188

Cited by 19 publications

(13 citation statements)

References 88 publications

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“…Antigen‐specific T cells in NMOSD and MOGAD have been seldom detected despite central dogma for the necessity of these cells in their role for autoantibody production and pathogenicity. Interestingly, AQP4‐specific CD4 + T cells were detected in AQP4 Ab‐positive patients, with T cell reactivity observed in a peptide sequence at amino acids 156–170 which overlaps with the epitope recognised by AQP4 Ab 113,114 . Contrastingly, the same study could not detect MOG‐specific T cells in MOG Ab‐positive patients and this was postulated to be because of the failure of synthetic peptides in mimicking antigen processing and MHC presentation 113 .…”

Section: Pathogenic Mechanisms In Autoimmune Demyelinationmentioning

confidence: 91%

“…Interestingly, AQP4-specific CD4 + T cells were detected in AQP4 Ab-positive patients, with T cell reactivity observed in a peptide sequence at amino acids 156-170 which overlaps with the epitope recognised by AQP4 Ab. 113,114 Contrastingly, the same study could not detect MOG-specific T cells in MOG Ab-positive patients and this was postulated to be because of the failure of synthetic peptides in mimicking antigen processing and MHC presentation. 113 Indeed, a previous study using Escherichia coli-expressed MOG coupled to fluorescent beads was able to detect MOG-specific CD4 + T cells producing IFNgamma, IL-22 and IL-17A in 16 out of 29 MS patients.…”

Section: T Cellsmentioning

confidence: 96%

“…113,114 Contrastingly, the same study could not detect MOG-specific T cells in MOG Ab-positive patients and this was postulated to be because of the failure of synthetic peptides in mimicking antigen processing and MHC presentation. 113 Indeed, a previous study using Escherichia coli-expressed MOG coupled to fluorescent beads was able to detect MOG-specific CD4 + T cells producing IFNgamma, IL-22 and IL-17A in 16 out of 29 MS patients. 115 However, MOG Ab was detected in only one of these patients reinforcing the notion that MOG Ab seropositivity in MS patients is rare and that the role of MOG-specific T cells in MS patients remains difficult to explore.…”

Section: T Cellsmentioning

confidence: 96%

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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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Section: Pathogenic Mechanisms In Autoimmune Demyelinationmentioning

confidence: 91%

Section: T Cellsmentioning

confidence: 96%

Section: T Cellsmentioning

confidence: 96%

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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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“…In addition, patients seropositive for both AQP4 and MOG antibodies have been reported when detecting MOG-Abs by ELISA, while double seropositivity is not common when utilizing CBAs (41). Moreover, whether MOG antigen or MOG-Abs participate in NMOSD pathogenesis is needed to be further clarified, as one recent research has found that a role of AQP4-specific, but not MOG-specific T-cells, in NMOSD (51).…”

Section: Mog-abs In Neuromyelitis Optica Spectrum Disordermentioning

confidence: 99%

Evolution in anti-myelin oligodendrocyte glycoprotein antibody detection and its clinical significance: a narrative review

Zhong¹,

Wang²,

Luo³

et al. 2023

Ann Transl Med

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Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressing on the surface of myelin sheaths and oligodendrocyte plasma membrane in the central nervous system of mammals, and it has a highly conserved nucleotide and amino acid structure between species. Evidence from animal research support that anti-MOG antibodies (MOG-Abs) are pathogenic antibodies rather than a bystander secondary to myelin destruction. Similarly, immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a demyelinating disease-associated autoantibody in human beings. In clinical studies, several detection methods, including ELISA, immunoblot, radio immunoprecipitation assays and Cellbased assays (CBAs), have been applied in identifying MOG-Abs in idiopathic inflammatory demyelinating diseases (IIDDs) of human beings. CBAs method is recommended by many proposed diagnostic criterions for MOG-Abs-associated disorders (MOGAD). This method involves transfection of mammalian cells with MOG antigen, binding of MOG-Abs to MOG antigen, binding of secondary antibodies to MOG-Abs and quantification method. However, the reliability for CBAs systems of MOG-Abs detection can be influenced by numerous factors, such as length of MOG antigen, expression vectors, cell lines, secondary antibodies, and read-out systems. In addition, there are controversial results on the studies of IIDDs with MOG-IgG positive. Nowadays, more and more evidence suggests that patients positive for MOG-IgG share common features, but further clinical and laboratory researches are needed to clarify if MOGAD is an independent disease entity. In this review, we intend to summarize the detection methods of MOG-Abs and their sensitivity and specificity to MOGAD in human.

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“…Intracortical demyelination was overrepresented in comparison to classical MS [ 47 ]. These pathological observations have to be contrasted with the fact that, to date, no MOG-specific T cells have been found in the peripheral blood of patients with MOGAD [ 48 ]. This could be explained by the fact that these MOG-specific T cells are difficult to detect due to their low frequencies.…”

Section: Immunopathogenesismentioning

confidence: 99%

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

Derdelinckx

Reynders

Wens

et al. 2021

IJMS

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Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clinical trials or have been used as rescue treatment in treatment-refractory cases. The development of antigen-specific cell-based immunotherapies for autoimmune diseases is slowed down by the rarity of the diseases, the lack of surrogate outcomes and biomarkers that are able to predict long-term outcomes and/or therapy effectiveness as well as challenges in the manufacturing of cellular products. These challenges are likely to be overcome by future research.

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Comparative Analysis of T-Cell Responses to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in Inflammatory Demyelinating Central Nervous System Diseases

Cited by 19 publications

References 88 publications

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

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

Evolution in anti-myelin oligodendrocyte glycoprotein antibody detection and its clinical significance: a narrative review

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

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