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- W4379517866 abstract "Background In spite of advancements in treatment of ankylosing spondylitis (AS), its pathogenesis remains incompletely understood. The current evidence suggests that AS is both an autoinflammatory and autoimmune disease involving innate immune cells along with autoreactive lymphocytes. B cells have received little attention regarding their role in the pathogenesis of ankylosing spondylitis (AS), although the available evidence shows presence of B cells at inflammatory sites, imbalances in B cell subsets, presence of autoantibodies (anti-CD74/CLIP), and beneficial effects of B cell depletion (anti-CD20) with rituximab [1]. In AS, the overarching picture portrays increased B cell activation, although it is unclear whether B cells directly affect pathogenesis, or are merely bystanders in the disease process. Objectives Our main objective was to study gene expression and gene signalling pathways involved in B cell activation in AS. To this end, we analysed the transcriptomic profile of isolated peripheral B cells from AS patients, healthy donors (HD) and patients with primary Sjögren syndrome (pSS), a typical B-cell-associated autoimmune disease. Methods RNA was isolated from CD19 + B cells sorted from peripheral blood mononuclear cells of 8 AS patients (mean age 48.0 ± 9.7 years, 63% male, mean ASDAS 2.5 ± 0.7), 8 sex and age-matched HDs (42.3 ± 17.8 years, 63% male) and 8 age-matched pSS patients (48.4 ± 17.8 years, 13% male). Next, characterization of differentially expressed genes was performed using transcriptomic analysis by the NanoString nCounter Autoimmune Profiling Panel, which utilizes a direct hybridization technique without PCR amplification. After normalization and z-score scaling of pathway genes, pathway scores were calculated based on the first principle component using nCounter advanced analysis software. P-values <0.05 were considered significant. Results All samples passed quality control, except for one pSS patient sample that was being flagged as an outlier by the nCounter advanced analyses software. Analysis of differential gene expression between AS patients and HDs revealed upregulation of 8 genes, including MAPK14 , KMT2A and PKM , in B cells from AS patients, and downregulation of two genes, DDIT4 and ATG5 . In AS patients, the relative expression of B cell receptor (BCR) signalling (n=60 genes) and Fc receptors and phagocytosis (n=55 genes) pathway genes were both significantly enriched compared to HDs ( Figure 1 ). Although not significant, these pathways also displayed higher pathway scores in pSS patients compared to HDs (P=0.30 and P=0.37, respectively). Other gene pathways involved in B cell activation, such as toll-like receptor signalling were not significantly enriched. Conclusion In this study, we observed several differentially expressed genes involved in signal transduction pathways in B cells from AS patients. Furthermore, we showed increased expression of gene pathways involved in B cell activation in patients with AS compared to HDs. The BCR-mediated activation in AS displays similarities to a bona fide autoimmune disease pSS. These results suggest active involvement of B cells in the disease process of AS. Reference [1]Wilbrink, R et al. (2021). B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis. International journal of molecular sciences . Figure 1. Gene pathway scores of (A) B cell receptor signalling and (B) Fc receptors and phagocytosis between AS, pSS patients and HDs. P-values <0.05 were considered significant. Acknowledgements: NIL. Disclosure of Interests Rick Wilbrink: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, Union Chimique Belge (UCB), Novartis, Frans G.M. Kroese Speakers bureau: BMS Roche and Jannsen-Cilag, Consultant of: BMS, Grant/research support from: unrestricted grants from BMS, Gwenny M. Verstappen: None declared." @default.
- W4379517866 created "2023-06-07" @default.
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- W4379517866 date "2023-05-30" @default.
- W4379517866 modified "2023-09-27" @default.
- W4379517866 title "POS0436 INCREASED EXPRESSION OF PATHWAYS INVOLVED IN B CELL ACTIVATION IN PATIENTS WITH ANKYLOSING SPONDYLITIS" @default.
- W4379517866 doi "https://doi.org/10.1136/annrheumdis-2023-eular.1192" @default.
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