B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping

Abstract

Background Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. Methods B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared. Results The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27+ memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score. Conclusions B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.

Deep Immunophenotyping of Circulating T and B Cells in Relapsing Adult-Onset Still’s Disease

“…It should be noted that IL-1β promotes B-cell activation, proliferation as well as differentiation into plasma cells [39], which may be closely related to high levels of this cytokine in AOSD during increased disease activity. In contrast, Fang et al showed that active AOSD is paralleled with an increased percentage of "naïve" IgD+CD27-B cells, double-negative IgD-CD27-B cells as well as CD20-CD27hi plasmablasts, whereas the "regulatory" B-cell subsets-IgD+CD27+ and CD24hiCD27+-significantly decreased [40].…”