THU0271 SERUM LEVELS OF TRANSFORMING GROWTH FACTOR î’ (TGF-î’) IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME
Authors: Maria Maślińska, Agnieszka Paradowska-Gorycka, Małgorzata Mańczak, Kinga Kostyra-Grabczak, Brygida Kwiatkowska
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Primary Sjogren's syndrome (pSS) is an autoimmune disease affecting primarily exocrine, especially salivary, glands. The epithelial damage, autoantigens release, activation of innate and acquired immunity form the underlaying of the pSS pathogenesis. The main role in pSS is played by B-lymphocytes and production of autoantibodies. One of the cytokines which may play a role in autoimmune processes is tumor growth factor beta (TGF-β), pleiotropic cytokine, which is involved in the control of autoimmune reactions, cell proliferation and the organ accumulation of lymphocytes. Numerous studies focused on the expression of TGF-β in salivary glands, as an organ targeted in pSS. <h3>Objectives</h3> The aim of this study was to evaluate the activity of TGF- β in serum of patients with pSS and to show its significant relationships with other cytokines active in the pathogenesis of this syndrome. <h3>Methods</h3> 33 patients with pSS (according to current EULAR/ACR criteria) were included into the study, female 28 (85%), men 5 (15%), mean age 47± SD=16. Routine laboratory tests (blood morphology, ESR, CRP, rheumatoid factor) were performed along with ophthalmological assessment (Schirmer's test, ocular staining score) with confirmation of dry eye. Patients had routine chest X-ray and, in case of clinical indications, high resolution computed tomography to assess interstitial changes. Serum concentrations of TGF-β were determined using an Quantikine ELISA Kit. Serum cytokines levels of BAFF, APRIL, FLT-3L, LT-α, IL-21, TNF-α were evaluated using standard ELISA assays. Level of antinuclear antibodies (IF;HEp-2000) was measured; presence of anti-SS-A and anti-SS-B antibodies was determined by semi-quantitative immunoblotting evaluation. Biopsy of minor salivary gland with the histopathological evaluation (focus score-FS) and the immunochemistry (CD3 +, CD4 +, CD19 +, CD21 +, CD35 + cells) was performed. Statistics: differences between groups were analyzed using U Mann-Whitney test (continuous variables). Correlations between quantative variables were assessed with the Spearman correlation coefficient. Statistical significance p&lt;0.05. The study was approved by the ethics committee. <h3>Results</h3> The negative correlation (rho = -0.472) between TGF-β and TNF-α was demonstrated. There was no correlation between TGF-β and other tested cytokines or autoantibodies (ANA, anti -SS-A, anti-SS-B). There was no correlation between TGF-β and results of ocular examinations, FS and immunochemistry. There was no correlation between TGF-β and lung involvement, especially fibrosis, in this group. Conclusion: i) results may indicate that TGF-β, influences the serum TNF-α activity in pSS patients, ii) our findings suggest, that TGF-β may be the strongest inhibitor of TNF-α among cytokines involved in pSS pathogenesis, iii) results may explain the ineffectiveness of anti-TNF drugs in the treatment of pSS <h3>References</h3> [1] Fechtner S, et al. Transforming growth factor β activated kinase 1: a potential therapeutic target for rheumatic diseases. Rheumatology (Oxford). 2016;56(7):1060-1068. [2] Zhou J, et al. Pathogenic role of endogenous TNF-α in the development of Sjögren's-like sialadenitis and secretory dysfunction in non-obese diabetic mice. Lab Invest. 2017;97(4):458-467. [3] Keystone EC. The utility of tumour necrosis factor blockade in orphan diseases. Ann Rheum Dis. 2004;63 Suppl 2(Suppl 2):ii79-ii83. <h3>Disclosure of Interests</h3> None declared