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 systemic sclerosis

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ID: 319285
2026
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Abstract
Abstract Objectives Although BAFF serum levels are reported to correlate with the extent of skin fibrosis and markers of systemic inflammation in systemic sclerosis, its relation with BAFF-R expression levels and 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. Methods PBMCs 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. Results BAFF levels were significantly elevated in SSc patients compared with controls. This was more pronounced in clinically active than clinically stable patients, and in ATA+ compared with 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 erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in ATA+ SSc patients. Of note, we observed a moderate correlation between BAFF and ATA-IgG, but not between BAFF and ACA-IgG. Conclusions Our 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.
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Authors A M Alzahrani, S F H Neys, W M van Oostveen, Saad Ahmed, E W N Levarht, R W Hendriks, O B J Corneth, H U Scherer, R E M Toes, J K de Vries-bouwstra, Cynthia M. Fehres
Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag354
URL
https://doi.org/10.1093/rheumatology/keag354
Keywords Keywords not found

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