THU0217 SERUM THYMIC STROMAL LYMPHOPOIETIN (TSLP) AS A BIOMARKER OF B-CELL LYMPHOPROLIFERATION IN SJÖGREN’S SYNDROME
Authors: Saviana Gandolfo, Cinzia Fabro, Michela Bulfoni, Elena Doriguzzi Breatta, Daniela Cesselli, Carla DI Loreto, Salvatore De Vita
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Thymic stromal lymphopoietin (TSLP) has been demonstrated to be expressed on salivary glands (SG) biopsies of patients with primary Sjögren's syndrome (pSS), mainly in more advanced degrees of lymphoproliferation and in B-cell MALT lymphoma tissues in pSS (1). <h3>Objectives:</h3> To study serum TSLP in a larger number of pSS patients, to confirm its correlation with the already studied tissue expression, and then to investigate a possible role of TSLP not only as a tissue biomarker, but also as a peripheral blood biomarker. <h3>Methods:</h3> Serum TSLP levels were assessed by ELISA in sera collected from ninety-one anti-SSA-positive pSS patients (females n=86, 94.5%; mean age 57.2 years, range 25-80), fulfilling the 2016 ACR-EULAR pSS classification criteria, 80 matched healthy blood donors (HBDs) and 21 patients with non-autoimmune sicca syndrome (nSS). pSS patients were then stratified according to the degree of lymphoproliferation (2), well previously defined by tissue studies in the same patients, as follows: pSS fully benign (fbSS), pSS with myoepithelial sialadenitis (MESA), and pSS B-cell MALT lymphoma (NHL); the difference in serum TSLP levels was studied between these three subgroups. In addition, prospective serum samples, collected both at the time of MESA diagnosis and later at the time of NHL development in the same patient, were studied in 3 cases. All the pSS patients were naïve to immunosuppressants, biotechnological drugs, chemotherapies, and were not receiving steroids at the time of sample collection. The most relevant features of pSS linked to a heavier mucosa-associated lymphoid tissue (MALT) involvement and lymphoproliferation, i.e. persistent parotid swelling and mixed cryoglobulinemia, were recorded, as well as the pathologic evidence of ectopic germinal centres (GCs) in SG biopsy. EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) was calculated for all the pSS patients. <h3>Results:</h3> Serum TSLP was significantly higher in pSS (mean 47.19 pg/mL, range 0-324.89) compared to nSS (mean 2.74 pg/mL, range 0-15.9) (p&lt;0.0001) and to HBDs controls (mean 0.59 pg/mL, range 0-11.09: very low levels being detected only in 4/80) (p&lt;0.0001). The significance was the same (p&lt;0.0001) also after excluding NHL pSS patients. Serum TSLP showed a progressive, significant increase from patients with fbSS (n=65; mean 26.54 pg/mL; range 0-75.11) to MESA (n=14; mean 69.72 pg/mL; range 20.62-140.8) (MESA vs fbSS p&lt;0.0001) and finally to NHL (n=12; mean 151.96 pg/mL; range 58.16-324.89) (NHL vs fbSS p&lt;0.0001; NHL vs MESA p=0.009). In prospective sera, TSLP levels significantly increased in all the 3 pSS patients from MESA to NHL. pSS patients showing a heavier involvement of MALT, i.e. with persistent parotid swelling, mixed cryoglobulinemia, or GCs in SG biopsy, showed significantly higher TSLP serum levels compared to pSS patients without this heavier MALT involvement. A significant correlation between higher TSLP serum levels and increasing ESSDAI was finally found (p&lt;0.0001). <h3>Conclusion:</h3> Serum TSLP could represent a novel biomarker of pSS-related B-cell lymphoproliferation, characterized by a heavier MALT involvement. The validation of the present monocentric results is currently ongoing within the EU HarmonicSS Project. <h3>References:</h3> [1] Gandolfo S. et al, Arthritis Rheumatol. 2017; 69 (suppl 10). [2] De Vita S. et al. Blood Cells Mol Di. 2001;27:757-66. <h3>Disclosure of Interests:</h3> Saviana Gandolfo: None declared, Cinzia Fabro: None declared, Michela Bulfoni: None declared, Elena Doriguzzi Breatta: None declared, Daniela Cesselli: None declared, Carla Di Loreto: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche