Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: There is an emerging view that mast cells may play a pivotal role in several inflammatory and autoimmune diseases. However, the role of mast cells in Sjögren’s syndrome remains unclear. We examined whether mast cells play a critical role in immune-mediated inflammation and fibrosis in patients with Sjögren’s syndrome.
Labial salivary gland samples were collected from 22 individuals with primary Sjögren’s syndrome and 10 with sicca syndrome (controls) and were examined using histological and immunohistochemical methods.Saliva production was evaluated by Saxon’s test. Mast cell density in the minor salivary glands was calculated at x400 magnification. Five fields were counted in all cases. The lymphocyte focus score was evaluated based on the number of inflammatory cell aggregates containing >50 lymphocytes per 4 mm2. The degree of fibrosis in the minor labial salivary glands was graded on a quantitative scale as previously reported (Clin Exp Rheumatol.1998;16:63-65). We used immunohistochemistry to identify and quantify tryptase-positive mast cells and vimentin-positive fibroblasts. Fibrous tissue was identified using elastic Van Gieson (EVG) staining. Human mast cell line 1 (HMC-1) cells were cocultured with pulmonary fibroblasts for 7 days using a transwell system, and type I collagen synthesis in fibroblasts was evaluated by quantitative RT-PCR.
Results: We found that the number of mast cells in the labial salivary glands of patients with primary Sjögren’s syndrome was significantly increased compared to that in control subjects (p<0.0001). There was a significant negative correlation between the Saxon’s test results and the number of mast cells (r= -0.6742, p=0.006), suggesting the involvement of mast cells in the decreased salivary secretion. There was no significant correlation between the intensity of lymphoid infiltration assessed by the focus score and the mast cell density (r=0.01545, p=0.58). In contrast, a significant correlation between the number of mast cells and the degree of fibrosis was observed (r= 0.5911, p=0.0038). Consistent with these findings, histochemical analysis revealed that mast cells were usually present in close proximity to EVG-stained fibrous tissue in the labial salivary glands. Furthermore, double immunostaining revealed that the mast cells were located proximal to vimentin-positive fibroblasts. We hypothesized that mast cells were involved in the development of tissue fibrosis via modulation of fibroblast immune function in sialadenitis and conducted an in vitro co-culture of HMC-1 cells and pulmonary fibroblasts. Significant up-regulation of Col1a mRNA was observed in fibroblasts co-cultured with HMC-1 cells compared to that in fibroblast monocultures (p=0.02).
Conclusion: These results suggest a novel role for mast cells in the development of sialadenitis in patients with primary Sjögren’s syndrome by induction of tissue fibrosis via fibroblast collagen synthesis.
To cite this abstract in AMA style:Kaieda S, Fujimoto K, Tominaga M, Okamoto M, Hoshino T, Ida H. Involvement of Mast Cells in the Pathogenesis of Sjögren’s Syndrome By Induction of Tissue Fibrosis Via Fibroblast Collagen Synthesis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/involvement-of-mast-cells-in-the-pathogenesis-of-sjogrens-syndrome-by-induction-of-tissue-fibrosis-via-fibroblast-collagen-synthesis/. Accessed January 20, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/involvement-of-mast-cells-in-the-pathogenesis-of-sjogrens-syndrome-by-induction-of-tissue-fibrosis-via-fibroblast-collagen-synthesis/