Abstract
Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of diseases. The appearance of antinuclear antibodies (ANAs) in almost half of the patients suggests B cell dysregulation as a distinct pathomechanism in these patients. Additionally, ANAs were considered potential biomarkers encompassing a clinically homogenous subgroup of JIA patients. However, in ANA+ JIA patients, the site of dysregulated B cell activation as well as the B cell subsets involved in this process is still unknown. Hence, in this cross-sectional study, we aimed in an explorative approach at characterizing potential divergences in B cell differentiation in ANA+ JIA patients by assessing the distribution of peripheral blood (PB) and synovial fluid (SF) B cell subpopulations using flow cytometry. The frequency of transitional as well as switched-memory B cells was higher in PB of JIA patients than in healthy controls. There were no differences in the distribution of B cell subsets between ANA- and ANA+ patients in PB. However, the composition of SF B cells was different between ANA- and ANA+ patients with increased frequencies of CD21lo/−CD27−IgM− “double negative” (DN) B cells in the latter. DN B cells might be a characteristic subset expanding in the joints of ANA+ JIA patients and are potentially involved in the antinuclear immune response in these patients. The results of our explorative study might foster further research dissecting the pathogenesis of ANA+ JIA patients.
Highlights
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood and affects joints and frequently eyes [1]
JIA patients were recruited into two independent studies: the first study aimed at analyzing the distribution of peripheral blood (PB) B cell populations, whereas the second study aimed at analyzing the distribution of synovial fluid (SF) B cell populations
The flow cytometric analysis of PB B cells in JIA patients was performed in the time period 2009–2010 in parallel to a cohort of healthy control individuals from which reference values for PB B cell subsets had been established [22]
Summary
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood and affects joints and frequently eyes [1]. CD21lo/− B cells are characterized by expression of the transcription factor T-bet as well as the chemokine receptors/integrin CXCR3 and CD11c They accumulate in inflamed tissues and seem to be enriched in autoreactive B cell clones [7, 8, 10]. CD21lo/− B cells that have undergone isotype switch (IgD and IgM negative) but did not upregulate the B cell memory marker CD27 have been described as a distinct B cell subset called “atypical memory” or “double negative” (DN) B cells. Those cells may be expanded in autoimmune diseases [9, 11, 12]
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