Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.
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 articleSubject
AutoimmunityHuman
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
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https://hdl.handle.net/10161/10224Published Version (Please cite this version)
10.1016/j.jaut.2013.12.005Publication 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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Show full item recordScholars@Duke
Jeffrey Guptill
Adjunct Associate Professor in the Department of Neurology
Vern Charles Juel
Professor of Neurology
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.
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
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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