Disease activity and anti-topoisomerase I antibody positivity are associated with elevated serum B cell activating factor levels and a B cell subset-wide reduction of BAFF-receptor expression in SSc.

objectivesAlthough B cell activating factor (BAFF) serum levels are reported to correlate with the extent of skin fibrosis and markers of systemic inflammation in SSc, their relationship with BAFF-receptor (BAFF-R) expression levels and their potential as biomarker for active disease is not investigated so far. This study was undertaken to investigate BAFF/BAFF-R dynamics in SSc and how they relate to autoantibody subtype and disease activity.

methodsPeripheral blood mononuclear cells of 69 SSc patients (ACA+: n = 37; ATA+: n = 32) and 10 age- and sex-matched controls were stained for BAFF-R followed by flow cytometry analyses. Serum BAFF and autoantibody levels were measured by ELISA.

resultsBAFF levels were significantly elevated in SSc patients compared with the controls. This was more pronounced in clinically active than clinically stable patients, and in ATA+ compared with the controls and ACA+ SSc patients. Concurrently, BAFF-R expression was reduced on total and on several B cell subsets. BAFF-R expression correlated inversely to serum BAFF levels. In addition, BAFF levels correlated with ESR and CRP in ATA+ SSc patients. Of note, we observed a moderate correlation between BAFF and ATA-IgG, but not between BAFF and ACA-IgG.

conclusionsOur study indicates that elevated BAFF levels, coupled with a reduction in BAFF-R expression, are significant characteristics in ATA+ SSc and of clinically active patients regardless of autoantibody status. Furthermore, BAFF levels show correlations with markers of systemic inflammation and autoantibody levels, specifically in ATA+ SSc. These findings might indicate distinct regulation of B cell responses in ATA+ and ACA+ SSc, particularly emphasizing their relevance in the context of clinically active SSc.