POS0788 DISTINCT CYTOKINE/CHEMOKINE PROFILE IN SJÖGREN’S SYNDROME IS ASSOCIATED WITH DISEASE ACTIVITY AND CLINICAL MANIFESTIONS

Background Sjögren’s syndrome (SjS) is an autoimmune disease of unknown aetiology. Several cytokines, chemokines and collagenases have been implicated in the pathogenesis of the disease. Nonetheless, biomarkers of diagnosis, outcome and response to treatment are still lacking. Objectives We aimed at evaluating potentially pathogenic cytokines/chemokines in a monocentric cohort of SjS patients. Methods Sera were drawn from SjS patients classified according to 2016 ACR/EULAR criteria and 23 cytokines/chemokines (CCL2/MCP-1, IP-10/CXCL10, Flt3 Ligand, IFNa2, IL6, IL7, IL12, IL13, IL15, IL17A, TNFa, IL-1Ra, CXCL13, IL21, IL23, IL33, TSLP, IL-2RA, IL1RII, TNFRII, BAFF, CCL19/MIP-3B 66, MMP-8) were quantified using Luminex multiplex immunoassay (BioRad- BioPlex 200 System-Luminex-Map technology R&D Systems, USA) following the manufacturer’s instructions and customized procedures. Data were acquired using Bioplex manager v 6.1. P value ≤ 0.05 was considered significant. Data were analyzed using GraphPad Prism V.8 (GraphPad Software, Inc.) software. Results Clinical and demographic features of 21 SjS patients are reported in Table 1. Our main findings were that several cytokines positively correlated with indexes of disease activity. Particularly, we observed a correlation between IL-2RA and ESSDAI (r=0.602, P=0.005) and between IL-12p40 and ESSPRI (r=0.674, P=0.016) (Figure 1). Levels of IL-17A seem to be influenced by age (r=0.622, P=0.039) and showed a trend towards a positive correlation with labial salivary gland biopsy focus score (r=0.942, P=0.058). The only patient with cryoglobulins was the male who showed levels of BAFF/BLyS >20x higher than the remaining 20 females (43.4 ng/ml vs 1.8±1.6 ng/ml). Table 1. N % Sex 1M/20F 4.8/95.2 Age (years, mean±SD) 53.43±12.27 disease duration (months, mean±SD) 30.29±10.47 ESSDAI (mean±SD) 2.20±2.40 ESSPRI (mean±SD) 4.18±2.12 Global dryness VAS (0-10) (mean±SD) 5.00±2.32 VAS fatigue (0-10) mean±SD) 4.00±2.39 VAS pain (0-10) (mean± SD) 3.48±3.28 Dry mouth 15 71.40 Dry eyes 17 81 Parotid Gland Swelling 4 19 Articular involvement 6 28 .6 Skin Involvement 1 4.7 Raynaud’s Phenomenon 5 23.8 Other Organs 3 14.3 Lymphoma 1 4.7 Low Complement (C3 Or C4) 3 14.3 Low C3 3 14.3 Low C4 1 4.7 Leukopenia 7 33.3 Hypergammaglobulinemia 7 61.9 Monoclonal Gammopathy 2 10 Ana 19 90.5 Anti-SSA 19 90.5 Anti-SSB 10 47.6 Rheumatoid Factor 9 42.9 Cryoglobulins 1 4.7 Salivary Gland Biopsy Focus Score (Mean±SD) 1.99±1.45 Hydroxychloroquine 5 23.8 Immunosuppressant 1 4.7 Figure 1. Conclusion For the first time we suggest the potential usefulness of IL-2RA as a marker of disease activity in SjS. Notably, IL2RA has been used as a marker to identify CD4+FoxP3+ regulatory T cells. So far, it is known that T follicular helper (Tfh) cell differentiation is inhibited by IL-2 while regulatory T cell differentiation and survival depend on it. Nonetheless, Wing et al. (1) described a CD25- subpopulation within human PD1+CXCR5+Foxp3+ Tfh cells preferentially located in germinal centers which is reduced by the presence of IL-2, possibly explaining the association with disease activity. IL-12p40 is known to have a pathogenic role in SjS (2) and we suggest that it may represent a complementary tool in the evaluation of patients’ symptoms. The presence of high levels of IL-15 in SjS is not novel and associated with T cell migration and proliferation in germinal centers. Finally, the observation of very high BAFF/BLyS levels in the male with cryoglobulins will require further analysis. References [1]Wing et al. Proc Natl Acad Sci USA. 2017 [2]Mathsson L, et al. Clin Exp Immunol. 2007 Disclosure of Interests None declared