Soluble BDCA-2 as a potential biomarker for rheumatoid arthritis and its role in enhancing IFN-α production through nucleic acid binding
Mainieri L, Kaufmann A, Bucci L, Grieshaber Bouyer R, Bauer S, Venegas-Solis F (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 65
Article Number: keaf537
Journal Issue: 1
DOI: 10.1093/rheumatology/keaf537
Abstract
Objectives: Aberrant interferon (IFN) signalling is strongly associated with rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Blood dendritic cell antigen 2 (BDCA-2) regulates IFN production in plasmacytoid dendritic cells (pDCs). While heparin inhibits IFN formation via triggering surface BDCA-2, its soluble form (solBDCA-2) antagonizes heparin and thereby drives excessive IFN formation. However, the role of solBDCA-2 in RA and SLE is unknown. This study aims to determine whether solBDCA-2 can serve as a biomarker for RA and/or SLE and provide insights into its potential role in disease mechanisms. Methods: solBDCA-2 and IFN-α expression were analysed by ELISA in the serum of RA (n=14) and SLE (n=14) patients and compared with healthy controls (n=15). To gain mechanistic insight of solBDCA-2 in RA and SLE, we studied the interaction of solBDCA-2 with nucleic acids, its role in enhancing type I IFN production in the plasmacytoid dendritic cell line CAL-1 and in human peripheral blood mononuclear cells (hPBMCs). Results: IFN-α was upregulated in patient sera of both RA and SLE. In contrast, solBDCA-2 was exclusively upregulated in the serum of RA patients, but not in patients with SLE. solBDCA-2 interacted with phosphodiester CpG-oligodeoxynucleotides (ODN) 2006, a ligand of TLR9, and poly I:C, a ligand of TLR3, to form complexes that enhance type I IFN production in CAL-1 cells and hPBMCs. Conclusion: These findings show that solBDCA-2 enhances type I interferon production by forming immunostimulatory complexes with DNA and RNA. Dysregulated solBDCA-2 expression might contribute to RA pathogenesis.
Authors with CRIS profile
Laura Bucci
Department of Medicine 3 – Rheumatology and Immunology
Ricardo Grieshaber Bouyer
Professur für Klinische Systemimmunologie
Involved external institutions
Germany (DE)How to cite
APA:
Mainieri, L., Kaufmann, A., Bucci, L., Grieshaber Bouyer, R., Bauer, S., & Venegas-Solis, F. (2026). Soluble BDCA-2 as a potential biomarker for rheumatoid arthritis and its role in enhancing IFN-α production through nucleic acid binding. Rheumatology, 65(1). https://doi.org/10.1093/rheumatology/keaf537
MLA:
Mainieri, Lisa, et al. "Soluble BDCA-2 as a potential biomarker for rheumatoid arthritis and its role in enhancing IFN-α production through nucleic acid binding." Rheumatology 65.1 (2026).
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