Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by fibroblasts activation, increased extra-cellular matrix synthesis associated with autoimmunity. However, the potential role of B lymphocytes in the pathophysiology of SSc is still poorly defined.
Methods: Phenotyping of peripheral blood B cell subpopulations, activating and inhibitory receptor expressions, Interleukin 6 (IL-6) and transforming growth factor-beta (TGF-β) productions were characterized by flow cytometry and multiplex assay. Fibroblasts proliferation rate and collagen production upon incubation with supernatants of B cell isolated from patients or healthy controls were assessed using XTT, BrdU, Ki67 immunofluorescence staining and collagen assay, respectively.
Eighty patients (including 18 males) with SSc fulfilling the ACR/EULAR criteria, (22 with diffuse SSc, dSSc and 58 with limited cutaneous SSc, lSSc), and 21 healthy controls (HC) were studied. The proportion of IgD– CD27+ B cells was significantly lower for SSc patients (Mean±SD 19.33%±11.85) as for HC (25.91%±11.25) (p=0.041). Increased proportions of B cells expressing CD69 (8.29%±7.77 vs 2.36%±2.29 p=0.0017) and CD95 (47.02%±19.82 vs 28.93%±11.21 (p=0.0004)) were found in both lSSc and dSSc. Compared to HC and lSSc, B lymphocytes from dSSc patients also presented with higher proportions of cells positive for CD5 (24.12%±7.93 for dSSc vs 14.09%±6.58 for lSSc (p=0.0296) and 14.21%±5.34 for HC), CD86 (39.89%±22.11 for dSSc vs 17.72%±13.98 for lSSc (p=0.0007) and 11.68%±11.09 for HC), IL-6R (33.64%±23.12 for dSSc vs 17.91%±13.62 for lSSc (p<0.0001) and 12.08±8.68 for HC) and IL-21R (32.55%±20.19 for dSSc vs 5.76%±4.40 for lSSc (p<0.0001) and 5.93%±3.29 for HC). Intracellular flow cytometry identified a significantly increased proportion of IL-6 (24.53%±6.69 vs 13.23%±4.71 (p<0.0001)) and TGF-β (18.38%±10.22 vs 6.31%±3.62 (p<0.0001)) positive B lymphocytes in patients with SSc as compared to HC. Using multiplex assay, increased production of IL-6 (314.3 pg/ml±317.8 vs 6.10pg/ml±2.58 (p=0.0007)) and TGF-β (1020pg/ml±569 vs 163.8pg/ml±98.69 (p=0.0011)) altogether with reduced production of IL-10 (8.67pg/ml±6.22 vs 333.1pg/ml±123.7 (p=0.0008)) were detected upon stimulation of B lymphocytes isolated from SSc patients compared to HC. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to HC.
Conclusion: We characterized a differential activation of peripheral B cells of patients exhibiting dSSc with an upregulation of CD5, CD86, IL-6R and IL-21R compare to lSSc patients and HC. B lymphocytes of SSc patients also expressed more CD69 and CD95 compare to HC. Peripheral B lymphocytes secreted both interleukin 6 and transforming growth factor-beta, and activated fibroblasts in patients with SSc.
To cite this abstract in AMA style:Dumoitier N, Lofek S, Regent A, London J, Chaigne B, Terrier B, Varin-Blank N, Mouthon L. Peripheral B Lymphocytes Secrete Both Interleukin 6 and Transforming Growth Factor-Beta and Potentiate Fibroblast Activation in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/peripheral-b-lymphocytes-secrete-both-interleukin-6-and-transforming-growth-factor-beta-and-potentiate-fibroblast-activation-in-systemic-sclerosis/. Accessed March 3, 2021.
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