Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.
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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.
Published Version (Please cite this version)
Guptill, Jeffrey T, John S Yi, Donald B Sanders, Amanda C Guidon, Vern C Juel, Janice M Massey, James F Howard, Flavia Scuderi, et al. (2015). Characterization of B cells in muscle-specific kinase antibody myasthenia gravis. Neurol Neuroimmunol Neuroinflamm, 2(2). p. e77. 10.1212/NXI.0000000000000077 Retrieved from https://hdl.handle.net/10161/10206.
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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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