title: 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.
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, 204 SORF (Bldg. 41), 915 S. LaSalle Street, Box 2926, Durham, NC 27710, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Yi
authors.affiliation: Neuromuscular Division, Department of Neurology, Duke University Medical Center, DUMC Box 3403, Durham, NC 27710, USA.
authors.forename: A
authors.initials: A
authors.lastname: Guidon
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, 204 SORF (Bldg. 41), 915 S. LaSalle Street, Box 2926, Durham, NC 27710, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sparks
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, 204 SORF (Bldg. 41), 915 S. LaSalle Street, Box 2926, Durham, NC 27710, USA.
authors.forename: R
authors.initials: R
authors.lastname: Osborne
authors.affiliation: Neuromuscular Division, Department of Neurology, Duke University Medical Center, DUMC Box 3403, Durham, NC 27710, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Juel
authors.affiliation: Neuromuscular Division, Department of Neurology, Duke University Medical Center, DUMC Box 3403, Durham, NC 27710, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Massey
authors.affiliation: Neuromuscular Division, Department of Neurology, Duke University Medical Center, DUMC Box 3403, Durham, NC 27710, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Sanders
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, 204 SORF (Bldg. 41), 915 S. LaSalle Street, Box 2926, Durham, NC 27710, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Weinhold
authors.affiliation: Neuromuscular Division, Department of Neurology, Duke University Medical Center, DUMC Box 3403, Durham, NC 27710, USA. Electronic address: jeffrey.guptill@duke.edu.
authors.forename: J T
authors.initials: JT
authors.lastname: Guptill
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D012737:Sex Factors; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Autoimmunity; Human; MuSK protein; Myasthenia gravis; Regulatory; T-lymphocytes