Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

Horellou, Philippe; Chalus, Aliénor de; Giorgi, Laetitia; Leroy, Carole; Chrétien, Pascale; Hacein‐Bey‐Abina, Salima; Bourgeois, Christine; Mariette, Xavier; Serguera, Ché; Grand, Roger Le; Deiva, Kumaran

doi:10.3389/fimmu.2021.679770

Cited by 8 publications

(8 citation statements)

References 54 publications

(57 reference statements)

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“…This general distribution of MOGAD phenotypes was also observed when assessing all identified studies (Table 1). Overall, 39 identified articles (including the six aforementioned incident cohort studies) reported the phenotype at initial presentation for 1,686 pediatric MOGAD patients 4–6,8,11–45 . Most of these studies were limited by the potential for selection bias in patient identification (e.g., patients with stored serum available for retrospective MOG‐Ab testing, relapsing disease course, etc.).…”

Section: Resultsmentioning

confidence: 99%

Attack phenotypes and disease course in pediatric MOGAD

Santoro

Beukelman²,

Hemingway

et al. 2023

Ann Clin Transl Neurol

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Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating condition that affects children differently than adults. We performed a literature review to assess the presentation and clinical course of pediatric MOGAD. The most common initial phenotype is acute disseminated encephalomyelitis, especially among children younger than five years, followed by optic neuritis (ON) and/or transverse myelitis. Approximately onequarter of children with MOGAD have at least one relapse that typically occurs within three years of disease onset and often includes ON, even if ON was not present at onset. Clinical risk factors for a relapsing course have not been elucidated.

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Section: Resultsmentioning

confidence: 99%

Attack phenotypes and disease course in pediatric MOGAD

Santoro

Beukelman²,

Hemingway

et al. 2023

Ann Clin Transl Neurol

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“…In patients with MOGNR at onset of the disease, we recently found a higher Th17 response to rh-MOG than in patients with MOGR. 12 Th17 has been associated with demyelinating diseases in children and adults during inflammatory events, 42 , 43 in particular in children with MOGAD. 13 In addition, Th17-related cytokines G-CSF and IL-6 levels are increased in MOGAD, 13 and IL-6 levels in CSF correlate with MOG antibody levels in paediatric patients with monophasic acquired demyelination syndromes.…”

Section: Discussionmentioning

confidence: 99%

“…CD4 + Foxp3 + T regs were significantly increased in response to rh-MOG in MOGNR, while CD45RA − Foxp3 + T regs decreased upon rh-MOG stimulation in relapsing MOGAD (MOGR) patients. 12 It was suggested that MOG Abs and MOG-autoreactive lymphocytes might be involved in MOG Abs-associated demyelination 13 and axonal damage. 14 We therefore decided to evaluate axonal injuries using biological markers in MOGR and MOGNR.…”

Section: Introductionmentioning

confidence: 99%

Early blood neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels associate with different disease courses of myelin oligodendrocyte glycoprotein-associated disease in children

Horellou

Flet‐Berliac

Leroy

et al. 2023

Brain Communications

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Acquired demyelinating syndrome associated with myelin oligodendrocyte glycoprotein antibodies, named recently myelin oligodendrocyte glycoprotein associated disease, represent more than 27% of this pediatric syndrome. Relapses occur in 40% of them which may be associated with severe outcomes. Aiming to identify biomarker allowing to predict relapse, we measured both myelin oligodendrocyte glycoprotein antibodies and neurofilament light chain levels in blood samples of patients which is known to reflect axonal injuries in neurological diseases including demyelinating autoimmune disorders. Three groups of patients were selected: relapsing myelin oligodendrocyte glycoprotein associated disease (n = 8), non-relapsing myelin oligodendrocyte glycoprotein associated disease (n = 7), and control patients with non-inflammatory neurological diseases (n = 12). Neurofilament light chain concentrations were measured in plasma of these 3 groups of patients using the high-sensitivity single-molecule array method at onset of the disease and 6 months later. At onset of the disease, we found that levels of neurofilament light chain in blood of none-relapsing patients were significantly higher than in control patients (means: 98.36 ± 22.66 vs 12.47 ± 2.47 pg/mL, ** P < 0.01, Kruskal–Wallis test). The mean neurofilament light chain value in relapsing patients (82.16 ± 38.41 pg/mL) was not significantly different from that in non-relapsing and in control patients. Plasma myelin oligodendrocyte glycoprotein antibodies levels were 2.5-fold higher in relapsing than in non-relapsing patients without reaching significance (means: 15.26 ± 4.87 vs 5.96 ± 1.13; two-tailed Mann-Whitney U-test P = 0.119). Plasma neurofilament light chain correlated significantly with myelin oligodendrocyte glycoprotein antibodies levels in relapsing (two-tailed Spearman r = 0.8, P = 0.0218) but not in non-relapsing (two-tailed Spearman r = 0.17, P = 0.71). Interestingly, the ratio of neurofilament light chain-to-myelin oligodendrocyte glycoprotein antibodies was significantly lower in relapsing than in non-relapsing patients (means: 5.19 ± 1.61 vs 21.87 ± 6.13; two-tailed Mann-Whitney U-test P = 0.014). These findings suggest that measuring both neurofilament light chain and myelin oligodendrocyte glycoprotein antibodies levels in patients at onset of demyelinating disease could predict relapse of myelin oligodendrocyte glycoprotein associated disease.

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“…Th17 responses are higher in MOGAD patients. Our lab used different MOG peptides for in vitro stimulation and showed MOGAD patients had more IL17+ and IL17+IFNγ+ (double positive) central memory cells than healthy controls (123). When relapse and remission MOGAD samples were compared, there was an increased proportion of IL17+, IFNγ+, and IL17+IFNγ+ CMCs after stimulation with several individual MOG peptides in MOGAD patients at the time of relapse (123) (72,113,125).…”

Section: T Cellsmentioning

confidence: 97%

“…Recently, a multinational study showed that IL6 receptor blockade with tocilizumab is therapeutically effective and safe in MOGAD and NMOSD (146). Increased TNFα, on the other hand, could also affect BBB permeability through We recently reported that A20, a negative regulator of the NF-κB pathway, is decreased in the serum during relapses on an individual level (123). Interestingly, steroids increase A20 expression in CD4 T cells.…”

Section: Biomarkers and Therapeutic Mechanismsmentioning

confidence: 99%

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease

Corbali

Chitnis

2023

Front. Neurol.

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Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is a spectrum of diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cerebral cortical encephalitis. In addition to distinct clinical, radiological, and immunological features, the infectious prodrome is more commonly reported in MOGAD (37–70%) than NMOSD (15–35%). Interestingly, pediatric MOGAD is not more aggressive than adult-onset MOGAD, unlike in multiple sclerosis (MS), where annualized relapse rates are three times higher in pediatric-onset MS. MOGAD pathophysiology is driven by acute attacks during which T cells and MOG antibodies cross blood brain barrier (BBB). MOGAD lesions show a perivenous confluent pattern around the small veins, lacking the radiological central vein sign. Initial activation of T cells in the periphery is followed by reactivation in the subarachnoid/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu, which enables T cells to infiltrate CNS parenchyma. CD4+ T cells, unlike CD8+ T cells in MS, are the dominant T cell type found in lesion histology. Granulocytes, macrophages/microglia, and activated complement are also found in the lesions, which could contribute to demyelination during acute relapses. MOG antibodies potentially contribute to pathology by opsonizing MOG, complement activation, and antibody-dependent cellular cytotoxicity. Stimulation of peripheral MOG-specific B cells through TLR stimulation or T follicular helper cells might help differentiate MOG antibody-producing plasma cells in the peripheral blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) in MOGAD support that most axonal damage happens in the initial attack, whereas relapses are associated with increased myelin damage.

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Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

Cited by 8 publications

References 54 publications

Attack phenotypes and disease course in pediatric MOGAD

Attack phenotypes and disease course in pediatric MOGAD

Early blood neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels associate with different disease courses of myelin oligodendrocyte glycoprotein-associated disease in children

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease

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