THU0043 The Alternative CD20 Transcript Variant is not Expressed in B Cells and Synovial Tissue from Patients with Rheumatoid Arthritis

ObjectivesMast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, their contribution remains controversial. To establish their role in RA, we analysed their presence in the synovium of treatment-naïve patients with early RA and their association and functional relationship with histological features of synovitis.MethodsSynovial tissue was obtained by ultrasound-guided biopsy from treatment-naïve patients with early RA (n=99). Immune cells (CD3/CD20/CD138/CD68) and their relationship with CD117+MCs in synovial tissue were analysed by immunohistochemistry (IHC) and immunofluorescence (IF). The functional involvement of MCs in ectopic lymphoid structures (ELS) was investigated in vitro, by coculturing MCs with naïve B cells and anticitrullinated protein antibodies (ACPA)-producing B cell clones, and in vivo in interleukin-27 receptor alpha (IL27ra)-deficient and control mice during antigen-induced arthritis (AIA).ResultsHigh synovial MC counts are associated with local and systemic inflammation, autoantibody positivity and high disease activity. IHC/IF showed that MCs reside at the outer border of lymphoid aggregates. Furthermore, human MCs promote the activation and differentiation of naïve B cells and induce the production of ACPA, mainly via contact-dependent interactions. In AIA, synovial MC numbers increase in IL27ra deficient mice, in association with ELS and worse disease activity.ConclusionsSynovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS.

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Selective Infiltration of B Cells Committed to the Production of Monoreactive Rheumatoid Factor in Synovial Tissue of Patients with Rheumatoid Arthritis

Clinical Immunology and Immunopathology ◽

10.1006/clin.1993.1144 ◽

1993 ◽

Vol 69 (1) ◽

pp. 16-22 ◽

Cited By ~ 10

Author(s):

Masayuki Hakoda ◽

Tsuyoshi Ishimoto ◽

Sakura Hayashimoto ◽

Kazuhiko Inoue ◽

Atsuo Taniguchi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Rheumatoid Factor ◽

Synovial Tissue

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Potential Biological Molecules and Immune Cell for Rheumatoid Arthritis Synovial Lesions

10.21203/rs.3.rs-491259/v1 ◽

2021 ◽

Author(s):

Mingyi Yang ◽

Yani Su ◽

Yao Ma ◽

Ke Xu ◽

Aihaiti Yirixiati ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Ontology ◽

Dendritic Cells ◽

B Cells ◽

Signaling Pathway ◽

Synovial Tissue ◽

Immune Cell ◽

Hub Genes ◽

Data Set ◽

Synovial Lesions

Abstract Objective: To study the potential biomarkers and related pathways in rheumatoid arthritis (RA) synovial lesions, as well as immune cell, to provide theoretical basis and research directions for the mechanism and treatment of RA. Methods: Download the RA synovial tissue microarray data set (GSE77298, GSE55457 and GSE55235) from Gene Expression Omnibus (GEO), The“limma” package of R to identify differentially expressed genes (DEGs), DAVIA Perform GO (Gene Ontology, gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes, Kyoto Gene Encyclopedia) enrichment analysis. STRING (Search Tool for the Retrieval of Interacting Genes) constructs a Protein Protein Interaction Network (PPI), R screens Hub genes, and mines targeted miRNAs of Hub genes based on multiple databases. In R,the immune cell of RA synovial tissue samples are obtained through the three packages of "e1071", "parallel" and "preprocessCore" with "CIBERSORT" software. Results: Ten Hub genes (KIAA0101, FOXM1, EGFR, CDC20, BUB1B, TYMS, TOP2A, RRM2, JUN and CCNA2) and 2 key miRNAs (miR-520d-5p and miR) related to RA synovial lesions were finally identified -139-5p), significantly enriched in epithelial cell signaling, ECM-receptor interaction, estrogen signaling pathway, cell cycle, ErbB signaling pathway and GnRH signaling pathway in Helicobacter pylori infection. Immune cell analysis found that resting dendritic cells, B cells memory, dendritic cells activated, plasma cells, macrophages M1, mast cells resting and T cells regulatory have high expression in RA, while neutrophils, B cells naive and natural killer cells activated have low expression in RA. Conclusion:The Hub genes, key miRNAs, related pathways, and immune cell obtained in this study provide a certain basis for the etiology and treatment of RA synovial lesions.

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THU0104 No expression of an alternative CD20 transcript variant in B cells from patients with rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-eular.2069 ◽

2013 ◽

Vol 71 (Suppl 3) ◽

pp. 189.2-189

Author(s):

M. Deschamps ◽

B. Gaugler ◽

P. Saas ◽

C. Ferrand ◽

E. Toussirot

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Transcript Variant

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POS0388 INTERLEUKIN 40 (IL-40) IS UP-REGULATED IN RHEUMATOID ARTHRITIS (RA) AND ASSOCIATED WITH DISEASE ACTIVITY, LEVELS OF AUTOANTIBODIES AND CHEMOKINES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2339 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 424.1-424

Author(s):

A. Navrátilová ◽

L. Andres Cerezo ◽

H. Hulejova ◽

V. Becvar ◽

D. Tegzová ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

Synovial Fluid ◽

Disease Activity ◽

B Cell ◽

Synovial Tissue ◽

Lupus Erythematosus ◽

Synovial Fibroblasts ◽

Clinical Activity

Background:Interleukin 40 (IL-40) is newly identified B cell - associated cytokine implicated in humoral immune responses and in B cell development. As B cells play a pivotal role in autoimmunity, we aimed to investigate the function of IL-40 in rheumatoid arthritis (RA).Objectives:The aim of our study was to determine the function of IL-40 in RA.Methods:IL-40 expression in the synovial tissue was determined by immunohistochemistry and immunofluorescence (n=4-5). IL-40 was analysed in the serum/synovial fluid of patients with RA (n=69), systemic lupus erythematosus (SLE; n=69), osteoarthritis (OA; n=44), and in healthy controls (HC; n=25). Given the association of IL-40 with B cells, we analysed the effect of rituximab therapy on the serum IL-40 in 19 patients with RA after 16 and 24 weeks of the therapy. The clinical activity of patients with RA was assessed according to the 28 joint count Disease Activity Score (DAS28). Levels of C-reactive protein (CRP) and autoantibodies were measured by routine laboratory techniques. In vitro experiments were performed in RA synovial fibroblasts (n=9). Levels of cytokines and inflammatory mediators were determined in serum, synovial fluid and supernatants using ELISA or multiplex immunoassay.Results:IL-40 was overexpressed in RA synovial tissue compared to OA, particularly by synovial fibroblasts and immune cells such as B and T lymphocytes, macrophages and neutrophils. The levels of IL-40 were significantly higher in the synovial fluid of RA patients compared to OA (33.2 (6.6-68.9) vs. 0.7 (0.1-2.4) ng/ml; p<0.0001). In addition, IL-40 was increased in the serum of RA patients compared to SLE, OA or HC (4.8 (1.7-24.9) vs. 1.4 (1.0-1.9), 1.6 (0.6-3.1) or 1.5 (0.7-2.7) ng/ml; p<0.0001 for all) and decreased after 16 (p<0.01) and 24 weeks (p<0.001) in a subgroup of rituximab treated patients with RA. IL-40 levels in RA patients correlated with autoantibodies rheumatoid factor (IgM) and anti-citrullinated protein antibody (ACPA) in the serum (p<0.0001 and p<0.01) as well as in the synovial fluid (p<0.0001 and p<0.001). IL-40 in RA synovial fluid was also significantly associated with DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), number of swollen joints (p<0.05) and neutrophil attractants IL-8 (p<0.01) and MIP-1α (p<0.01). RA synovial fibroblasts exposed to recombinant IL-40 increased secretion of IL-8 (p<0.01), MCP-1 (p<0.05) and MMP-13 (p<0.01) compared to unstimulated cells in in vitro conditions.Conclusion:Our results show for the first time that IL-40 is elevated in RA and decreases following B-cell depletion therapy. The association of IL-40 with autoantibodies and chemokines may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 by synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.Acknowledgements:Supported by MHCR 023728 a SVV 260 523Disclosure of Interests:None declared

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