Undiminished regulatory T cells in the thymus of patients with myasthenia gravis

Matsui, Naoko; Nakane, Shunya; Saito, Fumi; Ohigashi, Izumi; Nakagawa, Yasushi; Kurobe, Hirotsugu; Takizawa, Hisao; Mitsui, Takao; Kondo, Kenta; Kitagawa, Tetsuya; Takahama, Yousuke; Kaji, Ryuji

doi:10.1212/wnl.0b013e3181d31e47

Cited by 37 publications

(24 citation statements)

References 11 publications

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“…Furthermore, the frequency of circulating CD4 + CD25 high CD127 low/− Tregs did not appear to differ in treated vs. untreated MG patients. Our results are in agreement with a more recent study showing no significant alterations in the numbers of Treg cells in the peripheral blood of patients with MG [35], and similar studies showing no difference in the frequency of CD4 + CD25 high cells in patients with multiple sclerosis [36] and type 1 diabetes mellitus [37]. …”

Section: Discussionsupporting

confidence: 94%

Impaired regulatory function in circulating CD4+CD25highCD127low/− T cells in patients with myasthenia gravis

Thiruppathi

Rowin

Ganesh

et al. 2012

Clinical Immunology

103

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Previous studies have reported alterations in numbers or function of regulatory T cells (Tregs) in myasthenia gravis (MG) patients, but published results have been inconsistent, likely due to the isolation of heterogenous “Treg” populations. In this study, we used surface CD4, CD25high, and CD127low/− expression to isolate a relatively pure population of Tregs, and established that there was no alteration in the relative numbers of Tregs within the peripheral T cell pool in MG patients. In vitro proliferation assays, however, demonstrated that Treg-mediated suppression of responder T cells (Tresp) was impaired in MG patients and was associated with a reduced expression of FOXP3 in isolated Tregs. Suppression of both polyclonal and AChR-activated Tresp cells from MG patients could be restored using Tregs isolated from healthy controls, indicating that the defect in immune regulation in MG is primarily localized to isolated Treg cells, and revealing a potential novel therapeutic target.

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Section: Discussionsupporting

confidence: 94%

Impaired regulatory function in circulating CD4+CD25highCD127low/− T cells in patients with myasthenia gravis

Thiruppathi

Rowin

Ganesh

et al. 2012

Clinical Immunology

103

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“…The potential role of Tregs in the breakdown of self-tolerance in MG has been a focus of recent studies [63–65, 69–71]. The results of these studies have been somewhat mixed, likely due to heterogeneity of the patient populations studied and how Treg populations were defined.…”

Section: Discussionmentioning

confidence: 99%

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis

Guidon

Sparks

et al. 2014

Journal of Autoimmunity

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Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T-cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T-cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T-cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T-cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T-cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T-cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in Treg function or number.

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“…Напротив, ИЛ-4 обладает антагонистическим эффектом, пре-пятствует развитию симптомов миастении. Увеличе-ние уровня ИЛ-10 у пациентов с генерализованной формой миастении значимо выше, чем у пациентов с локальной формой [67,74,116].…”

Section: роль цитокинов в патогенезе миастении грависunclassified

“…Влияние T reg на патогенез аутоиммунных заболеваний, в том числе миастений, изучается ря-дом исследователей из разных стран. Исследователи предполагают, что функциональный дефицит клеток T reg может привести к неспособности подавить ауто-реактивные Т-клетки [65,67,109,114]. Воздействие на эти клетки, по данным некоторых исследователей, перспективное направление в те-рапии аутоиммунных расстройств.…”

Section: роль клеток иммунной системы в патогенезе миастении грависunclassified

Immunopathogenesis of Myasthenia Gravis (Review)

Gasymly¹

2018

Arhivʺ vnutr. med.

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Undiminished regulatory T cells in the thymus of patients with myasthenia gravis

Abstract: The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis.

Cited by 37 publications

References 11 publications

Impaired regulatory function in circulating CD4+CD25highCD127low/− T cells in patients with myasthenia gravis

Impaired regulatory function in circulating CD4+CD25highCD127low/− T cells in patients with myasthenia gravis

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis

Immunopathogenesis of Myasthenia Gravis (Review)

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