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

dc.contributor.author

Yi, JS

dc.contributor.author

Guidon, A

dc.contributor.author

Sparks, S

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Osborne, R

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Juel, VC

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Massey, JM

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Sanders, DB

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Weinhold, KJ

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Guptill, JT

dc.coverage.spatial

England

dc.date.accessioned

2015-06-16T19:33:36Z

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2014-08

dc.description.abstract

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 CD39 expression or Treg number.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/24378287

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S0896-8411(13)00152-2

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1095-9157

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https://hdl.handle.net/10161/10224

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

J Autoimmun

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10.1016/j.jaut.2013.12.005

dc.subject

Autoimmunity

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Human

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MuSK protein

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Myasthenia gravis

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Regulatory

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T-lymphocytes

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Adult

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Aged

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CD8-Positive T-Lymphocytes

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Cell Separation

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Cytokines

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Female

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Flow Cytometry

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Humans

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Immunoglobulin G

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Immunophenotyping

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Middle Aged

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Myasthenia Gravis

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Receptor Protein-Tyrosine Kinases

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Receptors, Cholinergic

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Sex Factors

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Th1 Cells

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Th17 Cells

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Young Adult

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Yi, JS|0000-0001-7777-2437

duke.contributor.orcid

Sanders, DB|0000-0003-2320-4965

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/24378287

pubs.begin-page

130

pubs.end-page

138

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Duke Clinical Research Institute

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Duke Human Vaccine Institute

pubs.organisational-group

Immunology

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Institutes and Centers

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Neurology

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Neurology, Neuromuscular Disease

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Pathology

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School of Medicine

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Surgery

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Surgery, Surgical Sciences

pubs.publication-status

Published

pubs.volume

52

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