Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.
Abstract
OBJECTIVE: To characterize B-cell subsets in patients with muscle-specific tyrosine
kinase (MuSK) myasthenia gravis (MG). METHODS: In accordance with Human Immunology
Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA
assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls.
To complement a B-cell phenotype assay that evaluated maturational subsets, we measured
B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody
titers. Immunologic variables were compared with healthy controls and clinical outcome
measures. RESULTS: As expected, patients treated with rituximab had high percentages
of transitional B cells and plasmablasts and thus were excluded from subsequent analysis.
The remaining patients with MuSK MG and controls had similar percentages of total
B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell
subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages
of B10 cells. In addition, we observed an increase in MuSK antibody levels with more
severe disease. CONCLUSIONS: We found prominent B-cell pathology in the distinct form
of MG with MuSK autoantibodies. Increased BAFF levels have been described in other
autoimmune diseases, including acetylcholine receptor antibody-positive MG. This finding
suggests a role for BAFF in the survival of B cells in MuSK MG, which has important
therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset
that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential
mechanism for the breakdown in immune tolerance in patients with MuSK MG.
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https://hdl.handle.net/10161/10206Published Version (Please cite this version)
10.1212/NXI.0000000000000077Publication Info
Guptill, Jeffrey T; Yi, John S; Sanders, Donald B; Guidon, Amanda C; Juel, Vern C;
Massey, Janice M; ... Weinhold, Kent J (2015). Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.
Neurol Neuroimmunol Neuroinflamm, 2(2). pp. e77. 10.1212/NXI.0000000000000077. Retrieved from https://hdl.handle.net/10161/10206.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
Kent James Weinhold
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
In addition to their ongoing HIV/AIDS-related research activities, the Weinhold Laboratory
is focused on utilizing a comprehensive repertoire of highly standardized and formerly
validated assay platforms to profile the human immune system in order to identify
immunologic signatures that predict disease outcomes. These ongoing studies span a
broad range of highly relevant clinical arenas, including: 1) cancer (non-small cell
lung cancer, head and neck cancer, glioblastoma neof
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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