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Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.

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Date
2015-04
Authors
Guptill, Jeffrey T
Yi, John S
Sanders, Donald B
Guidon, Amanda C
Juel, Vern C
Massey, Janice M
Howard, James F
Scuderi, Flavia
Bartoccioni, Emanuela
Evoli, Amelia
Weinhold, Kent J
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(11 total)
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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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Journal article
Permalink
https://hdl.handle.net/10161/10206
Published Version (Please cite this version)
10.1212/NXI.0000000000000077
Publication 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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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
Weinhold

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
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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