AB0163 THE ROLE OF IMMUNOREGULATORY MOLECULES ON FATIGUE IN PRIMARY SJöGREN’S SYNDROME
Authors: Kallpana Dhas, Emmanuella Traianos, Jessica Tarn, Wan Fai Ng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease characterized by exocrine gland dysfunction. The clinical presentation of pSS can vary considerably from predominantly 'sicca' symptoms such as dry eyes and dry mouth to systemic manifestations such as arthralgia, vasculitis and fatigue<sup>1,2</sup>. Previous work from our laboratory has suggested that immunoregulatory pathways might play a role in fatigue development in patients with pSS<sup>3</sup>. <h3>Objectives:</h3> The first aim was to measure the serum levels of three candidate immunoregulatory molecules (melatonin, TGF-β and IL-10) and determine any relationship with fatigue severity. The second aim was to compare molecular profiles of the immunoregulatory mediators between pSS patients and healthy controls. The third aim was to identify key predictors of fatigue in pSS. <h3>Methods:</h3> Serum levels of the three molecules were measured in 124 patients with pSS and 28 healthy non-fatigued controls selected from the United Kingdom Primary Sjögren's Syndrome Registry using various assays. IL-10 concentrations were measured using a cytometric bead array-based immunoassay, melatonin levels were determined using ELISA and TGF-β concentrations were quantified using a bioassay in which HKC-8 cells were stably transfected with a TGF-β inducible CAGA-luciferase reporter construct. Patient fatigue levels were evaluated with a validated self-complete questionnaire and the scores were compared with the immunoregulatory molecular levels using analysis of variance. Significance in immunoregulatory mediators between the patients and controls was determined using the Wilcoxon test. Ordinal logistic regression analysis was performed in a smaller subset of patients (N = 75) to identify the key predictors of fatigue in pSS. <h3>Results:</h3> IL-10 was significantly higher in the sera of patients with pSS compared to the healthy controls (p&lt;0.0001). Melatonin showed a positive correlation with fatigue levels within the patient cohort (ρ=0.1664) whereas IL-10 and TGF-β were inversely related to fatigue severity (ρ=0.1265 and ρ=0.0643 respectively). The regression model used the three investigated immunoregulatory molecules, disease specific, haematological and clinical parameters as well as patient reported depression, anxiety and pain as predictors. The model was able to predict fatigue levels to a 67% accuracy. <h3>Conclusion:</h3> The study suggests that melatonin may play a role in regulating the immune response in pSS and may affect fatigue levels in patients. Dryness, anxiety, pain and melatonin appear to be the most powerful predictors of fatigue in pSS. Further research into the effects of these immunoregulatory molecules is necessary to gain a better understanding of the pathophysiology of fatigue in pSS. <h3>References</h3> [1] Shahane A, Patel R. The epidemiology of Sjogren's syndrome. Clinical Epidemiology. 2014;6:247-255. [2] Ng W, Bowman S. Primary Sjogren's syndrome: too dry and too tired. Rheumatology. 2010;49(5):844-853. [3] Howard Tripp N, Tarn J, Natasari A, et al. Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines. RMD Open.2016;2(2):e000282. <h3>Disclosure of Interests:</h3> None declared