SAT0229 PROTEOMIC ANALYSIS REVEALS ASSOCIATION BETWEEN IMMUNE-METABOLIC BIOMARKERS AND CLINICAL SYMPTOMS IN SICCA PATIENTS
Authors: V. Pucino, J. D. Turner, F. Kollert, S. Rauz, A. Richard, J. Higham, A. Poveda-Gallego, S. J. Bowman, F. Barone, B. Fisher
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sjögren’s syndrome (SS) is a systemic autoimmune disease whose main characteristic is involvement of the exocrine glandular system. Thus, its most common clinical manifestation is eye and mouth dryness which, alongside fatigue and pain, contributes to poor health-related quality of life (HRQoL). A growing body of evidence recognises the adipose tissue as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders. A relationship between obesity and symptoms in SS has not yet been elucidated. Objectives: To explore potential associations between obesity-related immune-metabolic biomarkers and clinical symptoms in SS and sicca patients. Methods: Proteomics analysis of 184 cardio-immuno-metabolic proteins was assessed on sera from 53 SS (50 females (F), 3 males (M); mean age 54 years) and 60 sicca (56 F, 4 M; mean age 57 years) patients. Participants were enrolled in the Birmingham Optimising Assessment in Sjögren`s Syndrome (OASIS) cohort and examinations included the EULAR SS Patient Reported Index (ESSPRI), Schirmer’s test, unstimulated whole saliva, minor labial salivary gland biopsy, EuroQoL-5 dimension (EQ-5D) tool, immunological parameters, body max index (BMI) and Hb1Ac. Participants with SS fulfilled 2016 ACR/EULAR criteria. Non-SS sicca patients were anti-Ro antibody negative, displayed objective oral and/or ocular dryness, and did not have a physician diagnosis for SS. Linear regression analysis and univariate models were performed to identify the key predictors of symptoms. Results: HRQoL as measured as EQ-5D utility values, symptoms as assessed by ESSPRI, and BMI did not differ between the SS and sicca group. However, strong correlations between BMI (or fat or fat-free mass) and EQ-5D and ESSPRI scores were found in the sicca but not in the SS group. Among several proteins investigated, ADM, TNFRSF13B, FGF23, IL10RB, CD5, CD40, IL1RA, TNRSFN9, TNFRSF10A, TNFRSF11A, TRAILR2, GAL9, SPON2, ACE2, LEP, CD4, IL12B, SLAMF1, PD-L1 positively correlated with symptoms in the sicca group (R ≥ 0.3; Holm’s adjusted P ≤ 0.05). Adrenomedullin (ADM) showed the strongest correlation with ESSPRI (R = 0.56; P &lt; 0.0001); age (R = 0.45; P = 0.0003); BMI (R = 0.43, P = 0.0008); Ocular Surface Disease Index (R = 0.32, P = 0.03); EQ-5D utility value (R = -0.45, P = 0.001) and VAS patient (R = -0.41, P = 0.008). There was no association between ADM and gender, Schirmer`s test, disease and symptom duration (P &gt; 0.05). ADM was independently associated with ESSPRI scores in non-SS sicca patients when corrected for BMI, age, HbA1c, depression and anxiety scores. None of the above mentioned proteins correlated with clinical symptoms in the SS group. Conclusion: The study suggests that obesity-related immune-metabolic factors may play a role in regulating the symptoms in non-SS sicca patients. ADM appears to be a strong independent predictor of symptoms in these patients but not in SS. Disclosure of Interests: Valentina Pucino: None declared, Jason D. Turner: None declared, Florian Kollert Employee of: Novartis, Saaeha Rauz: None declared, Andrea Richard: None declared, Jon Higham: None declared, Ana Poveda-Gallego: None declared, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Francesca Barone: None declared, Benjamin Fisher: None declared