Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Calgizzarin (S100A11) is a member of the S100 protein family that acts in different tumors via regulating number of biologic functions. Recent data suggest its association with low grade inflammation in OA. The aim of the study was to analyze the expression of S100A11 in synovial tissue, synovial fluid and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to characterize its potential association with disease activity.
Methods: S100A11 expression was analyzed in synovial tissues from patients with RA (n=6) and OA (n=6) by immunohistochemistry. Immunofluorescence staining was used to co-localize S100A11 within RA synovial tissue (n=4). Serum and synovial fluid S100A11 levels were measured by ELISA (Biovendor) in 40 patients fulfilling the American College of Rheumatology criteria for the classification of RA and in 39 subjects with OA. Disease activity score based on 28 joints (DAS28-CRP) was used to assess disease activity. For in vitro experiments, peripheral blood mononuclear cells (PBMCs) and synovial fibroblasts (SFs) were obtained from patients with RA and OA (n=6-9). Expression and protein synthesis of S100A11 and cytokines were analyzed by RT-PCR, ELISA and Western Blot.
Results: The expression of S100A11 was significantly up-regulated in the synovial lining and sublining layers (p<0.01) and vessels (p<0.05) in patients with RA compared to OA and its expression was associated with fibroblasts, T lymphocytes and macrophages. Serum (14.13 [4.26-119.8] vs. 9.50 [4.95-30.16] ng/ml; p=0.004) and particularly synovial fluid (195.8 [20.22-974.2] vs. 28.40 [8.20-259.80] ng/ml; p<0.0001) S100A11 levels were significantly increased in patients with RA compared to OA. Moreover, the levels of S100A11 were higher in synovial fluid compared to serum in both RA and OA patients (p<0.0001). In patients with RA, synovial fluid S100A11 correlated significantly with DAS28 (r=0.350, p=0.027), CRP (r=0.463, p=0.003), synovial fluid leukocyte count (r=0.677, p<0.001), ACPA (r=0.424, p=0.006), but not with IgM-RF (r=0.059, p=0.719). No such associations were observed in serum. In addition, S100A11 is synthetized and spontaneously secreted in higher concentrations by PBMCs (p=0.01) and SFs (p=0.03) isolated from patients with RA in comparison with OA. Extracellular S100A11 protein stimulates the production of pro-inflammatory cytokines IL-6 and TNFα in PBMCs (p<0.05) and SFs (p<0.01).
Conclusion: Our data provide the first evidence of S100A11 up-regulation and its association with inflammation and disease activity in patients with RA. Acknowledgement: Supported by grant 15-34065A of the Agency for Healthcare Research of the Czech Republic and MHCR 023728.
To cite this abstract in AMA style:Andres Cerezo L, Šumová B, Prajzlerová K, Veigl D, Pavelka K, Vencovský J, Senolt L. S100A11 Protein Is Increased in Rheumatoid Arthritis and Is Associated with Disease Activity and Inflammation [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/s100a11-protein-is-increased-in-rheumatoid-arthritis-and-is-associated-with-disease-activity-and-inflammation/. Accessed January 19, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/s100a11-protein-is-increased-in-rheumatoid-arthritis-and-is-associated-with-disease-activity-and-inflammation/