title: B10 Cell Frequencies and Suppressive Capacity in Myasthenia Gravis Are Associated with Disease Severity.
abstract: Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disease. The mechanisms for loss of self-tolerance in this disease are not well understood, and recently described regulatory B cell (Breg) subsets have not been thoroughly investigated. B10 cells are a subset of Bregs identified by the production of the immunosuppressive cytokine, interleukin-10 (IL-10). B10 cells are known to strongly inhibit B- and T-cell inflammatory responses in animal models and are implicated in human autoimmunity. In this study, we examined quantitative and qualitative aspects of B10 cells in acetylcholine receptor autoantibody positive MG (AChR-MG) patients and healthy controls. We observed reduced B10 cell frequencies in AChR-MG patients, which inversely correlated with disease severity. Disease severity also affected the function of B10 cells, as B10 cells in the moderate/severe group of MG patients were less effective in suppressing CD4 T-cell proliferation. These results suggest that B10 cell frequencies may be a useful biomarker of disease severity, and therapeutics designed to restore B10 cell frequencies could hold promise as a treatment for this disease through restoration of self-tolerance.
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center , Durham, NC , USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Yi
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Russo
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Massey
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Vern
authors.initials: V
authors.lastname: Juel
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Hobson-Webb
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Karissa
authors.initials: K
authors.lastname: Gable
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Shruti M
authors.initials: SM
authors.lastname: Raja
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Balderson
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical Center , Durham, NC , USA.
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.affiliation: Department of Neurology, Neuromuscular Section, Duke University Medical Center , Durham, NC , USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Guptill
keywords: AChR; B10; Breg; IL-10; myasthenia gravis; regulatory B cells