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

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Date
2014-08
Authors
Yi, JS
Guidon, A
Sparks, S
Osborne, R
Juel, VC
Massey, JM
Sanders, DB
Weinhold, KJ
Guptill, JT
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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.
Type
Journal article
Subject
Autoimmunity
Human
MuSK protein
Myasthenia gravis
Regulatory
T-lymphocytes
Adult
Aged
CD8-Positive T-Lymphocytes
Cell Separation
Cytokines
Female
Flow Cytometry
Humans
Immunoglobulin G
Immunophenotyping
Middle Aged
Myasthenia Gravis
Receptor Protein-Tyrosine Kinases
Receptors, Cholinergic
Sex Factors
Th1 Cells
Th17 Cells
Young Adult
Permalink
https://hdl.handle.net/10161/10224
Published Version (Please cite this version)
10.1016/j.jaut.2013.12.005
Publication Info
Yi, JS; Guidon, A; Sparks, S; Osborne, R; Juel, VC; Massey, JM; ... Guptill, JT (2014). Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis. J Autoimmun, 52. pp. 130-138. 10.1016/j.jaut.2013.12.005. Retrieved from https://hdl.handle.net/10161/10224.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Guptill

Jeffrey Guptill

Adjunct Associate Professor in the Department of Neurology
Juel

Vern Charles Juel

Professor of Neurology
Massey

Janice Munn Massey

Professor of Neurology
Clinical Research in Neuromuscular diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, botulinum toxins, electromyography, dystonic disorders including cervical dystonia (spasmodic torticollis), limb focal dystonia, and blepharospasm.
Sanders

Donald Benjamin Sanders

Professor of Neurology
Research Interests: 1. Therapy of neuromuscular disease - immunologic and neuromuscular facilitating agents for myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). 2. Clinical trials in nerve, muscle and neuromuscular diseases
Yi

John S Yi

Adjunct Assistant Professor in the Department of Surgery
I am an immunologist, with a focus to characterize the immune system in response to infectious and non-infectious diseases including cancer, HIV, autoimmune disease, and transplantation. My goals are to identify novel biomarkers/immune signatures that clinicians can utilize to diagnosis, predict disease outcomes, and determine patients' response to treatment. 
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