Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Primary Sjögren’s syndrome (pSS) is an autoimmune and lymphoproliferative systemic disease with B cell hyperactivity and increased risk of non-Hodgkin lymphoma (NHL) evolution. In pSS, the salivary gland (SG) epithelium plays a crucial role in modulating the autoimmune response. Thymic stromal lymphopoietin (TSLP) is an epithelial lymphopoietic cytokine involved in the maintenance of immune tolerance at interfaces with the environment and in regulating lymphocyte homeostasis, acting also as a B cell growth factor. The aim of this study is to investigate TSLP expression in serum and SG biopsies, as well as TSLP function on peripheral blood lymphocytes (PBLs) in pSS patients, stratified according to their lymphoproliferative histopathologic status, from fully benign MALT lesions (fbSS) to myoepithelial sialadenitis (MESA) and to NHL.
Methods: Serum TSLP levels were determined by ELISA in 38 pSS patients (13 fbSS, 13 MESA, 12 NHL; all positive for the latest pSS ACR/EULAR Classification Criteria and for anti-SSA antibodies) and 33 controls (20 healthy blood donors, HBDs, and 13 non-autoimmune sicca, nSS). TSLP expression was also studied by RT-PCR and by immunohistochemistry in SG biopsies of all the pSS patients and nSS controls. Immunofluorescence double-staining was performed to characterize TSLP positive cells in SG. Correlations with clinical and histopathologic parameters were investigated. Finally, PBLs from both patients and controls were cultured and stimulated with TSLP and phenotypic changes evaluated by flow cytometry.
Results: TSLP serum levels were significantly higher in fbSS compared to nSS (p=0.048) and to HBDs (p<0.0001). A significant increase in TSLP levels occurred from fbSS to MESA (p=0.0015) and to NHL (vs fbSS p<0.0001; vs MESA p=0.0025), where the increase was dramatic. A positive significant correlation between serum TSLP and ESSDAI was found (p<0.0001). By contrast, in SG biopsies TSLP showed a pattern opposite to the serum by immunohistochemistry both in the salivary epithelium and in the whole inflammatory infiltrate: a significant declining staining of TSLP was in fact found from fbSS to MESA and NHL. Strikingly, however, the number of TSLP positive B cells progressively increased with the progression of lymphoproliferation, with the maximum number of TSLP positive B cells being detected in NHL. In vitro stimulation assays on cultured pSS PBLs showed a marked TSLP ability to promote proliferation and activation of B cells, and to induce IgG production.
Conclusion: A pathogenetic role of TSLP is herein suggested in pSS for the first time. Overall TSLP, which promotes B cell expansion, shows a progressive increase from benign to malignant B cell lymphoproliferation in pSS. The increasing serum levels of TSLP, coupled with the increasing expression by B cells themselves, may support a possible autocrine pathogenetic mechanism. By contrast, the observed decreasing production by the salivary epithelium suggests an insufficient response to regulate B cell expansion. Further studies are definitely worthwhile, including the analysis of TSLP as a biomarker to stratify pSS.
To cite this abstract in AMA style:Gandolfo S, Fabro C, Bulfoni M, Russi S, Quartuccio L, Sansonno DE, Di Loreto C, Cesselli D, De Vita S. Thymic Stromal Lymphopoietin (TSLP) Expression Is Associated with Lymphoproliferation and Lymphoma in Primary Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/thymic-stromal-lymphopoietin-tslp-expression-is-associated-with-lymphoproliferation-and-lymphoma-in-primary-sjogrens-syndrome/. Accessed July 28, 2021.
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