Background: Spondyloarthritis (SpA) comprises a heterogenous group of related chronic rheumatic immune-mediated diseases that are categorized into two main phenotypes: axial SpA (axSpA) and peripheral SpA (pSpA). The most common phenotype of pSpA is psoriatic arthritis (PsA). While innate immune cells and T cells are considered to play a central role in the pathogenesis of SpA, recent studies also suggest B cell involvement, at least in axSpA [1]. B cell infiltrates are observed at disease-affected sites in both radiographic axSpA (r-axSpA) and PsA patients. Furthermore, elevated serum levels of autoantibodies, such as anti-CD74 (IgA) in r-axSpA and anti-ADAMTS-L5 and anti-LL-37 (IgG) in PsA, point towards a potential role for B cells in the disease process of SpA. Whether the peripheral B cell compartment is altered in patients with pSpA remains controversial.

Objectives: To study the peripheral B cell compartment in-depth, including cell type composition and B cell receptor (BCR) responsiveness, in pSpA patients alongside r-axSpA patients and healthy controls (HCs).

Methods: Patients were included in this study if they had a confirmed diagnosis of pSpA or r-axSpA by a rheumatologist from tertiary referral centre. For the pSpA group, we primarily aimed to include patients with active peripheral manifestations. The pSpA patients were divided into PsA and the other clinical phenotypes of pSpA combined (e.g., undifferentiated SpA and inflammatory bowel disease associated SpA). Flow cytometry was used to analyse the circulating B cell subset composition in pSpA and r-axSpA patients compared to HCs. To measure BCR signaling responses, phosphorylation levels of Bruton’s tyrosine kinase (BTK; Y233), phosphoinositide 3-kinase (PI3K p85; Y458), and ribosomal S6 kinase (S6; S240/244) were measured in various B cell subsets upon anti-Ig stimulation using phosphoflow cytometry.

Results: A total of 116 study participants were included in this study: 42 PsA patients (mean age 54 years, 55% male), 30 patients with other pSpA subtypes (mean age 52 years, 40% male), 20 r-axSpA patients (mean age 51 years, 70% male), and 24 HCs (mean age 44 years, 54% male). Almost all patients with PsA and other pSpA subtypes exhibited active peripheral manifestations (peripheral arthritis, dactylitis, enthesitis) at the time of the study visit (83% and 90%, respectively), indicating active inflammation. In r-axSpA, active peripheral manifestations were observed in 35% of the patients. Approximately 70% of pSpA and 15% of r-axSpA patients used any disease-modifying antirheumatic drug at inclusion. In the peripheral blood of both patients with PsA or other pSpA subtypes, memory B cells (MBC) and double negative (DN; IgD ^- CD27 ^- ) B cells showed a shift towards IgA expression compared to HCs. Anti-Ig stimulation resulted in significantly enhanced phosphorylation of PI3K in IgA ⁺ DN as well as DN2 B cells (IgM ^- CD27 ^- CD21 ^- CD11c ⁺ ) from patients with PsA and other pSpA subtypes compared to HCs. Patients with pSpA also exhibited elevated levels of phosphorylated S6 in IgA ⁺ DN B cells and phosphorylated BTK in DN2 B cells after stimulation in comparison to HCs, reaching statistical significance for the PsA group only. A generally similar phosphorylation response pattern as in pSpA patients was seen in r-axSpA patients included in this study, although statistical significance in comparison to HCs was only reached for enhanced phosphorylated BTK levels in DN2 B cells from r-axSpA patients.

Conclusion: The shift towards IgA expression in circulating B cell subsets from pSpA patients, together with the aberrant BCR signaling response in (IgA ⁺ ) DN B cells, suggests enhanced mucosal immune responses in these patients and potential involvement of B cells in the disease process of pSpA.

REFERENCES: [1] Wilbrink, R.; Spoorenberg, A.; Verstappen, G.M.P.J.; Kroese, F.G.M. B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis. Int J Mol Sci 2021 , 22.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.