POS0433 CAN INTERLEUKIN 33 (IL-33) BE CONSIDERED A VALUABLE BIOMARKER IN THE EARLY STAGES OF SYSTEMIC SCLEROSIS? ANALYSIS OF A MONOCENTRIC COHORT
Authors: C. Angelelli, K. Stefanantoni, M. Cadar, G. Pellegrino, F. Conti, V. Riccieri
Journal: Annals of the Rheumatic Diseases (2021)

Background: The ScS approach has changed considerably in recent years especially concerning the very early diagnosis of the disease (VEDOSS) at the time when the patient is still in an undifferentiated form (UCTD) at risk of developing SSc (1, 2). Of great value are different clinical, instrumental and laboratory findings, such as specific autoantibodies and Nailfold VideoCapillaroscopy (NVC), able to identify those cases progressing into overt SSc. IL-33 cytokine is known to exert pro-fibrotic effects through its membrane receptor ST2 on immune cells and myofibroblasts and recent studies suggest that it can be released following endothelial cell activation at the onset of SSc (3, 4). Objectives: Our aim has been to evaluate IL-33 serum levels in a monocentric cohort of VEDOSS patients, looking for the possible association with clinical phenotype and disease progression, focusing on the microvascular capillaroscopic changes. Methods: Fourty-seven VEDOSS patients underwent a complete clinical, instrumental and laboratory evaluation, including NVC and specific SSc autoantibodies. At baseline serum IL-33 levels were measured using an ELISA assay. In 32 of them we also had a second serum sample at a follow-up time of at least 24 months (range 24 to 96 months). Results: During the follow-up time, 17 patients were subsequently reclassified as having ScS whereas 30 remained VEDOSS. The “progressor” subjects positively correlated with the presence of anti-Topoisomerase I antibodies (p&gt;0,004). IL-33 concentrations had a median value of 427.2 pg/ml (IQR 967.9 pg/ml) at baseline and of 130.4 pg/ml (IQR 399 pg/ml) at the follow up, showing a statistically significant difference independently from the progression of the disease (p=0.03). Besides significantly higher levels were detected in those patients with more severe NVC changes, defined as “active” pattern (p&lt;0.05). Among the 47 VEDOSS patients, 12 started some kind of vascular therapy. In these patients serum IL-33 concentrations significantly lowered during the follow-up respect to those without any treatment (p&lt;0.03) Conclusion: The analysis of our data confirms previous report (5) on higher IL-33 serum levels in the very early stages of UCTD patients at risk for SSc, regardless of their progression in established SSc, although related to more severe microvascular NVC involvement. The lowering of IL-33 serum levels that we detected in the follow up of our patients, may be linked to the well-known endothelial changes during the progression of the SSc and seems also to be partially affected by treatments. Investigation on a greater number of patients are needed to better understand our findings. References: [1]J. Avouac et al. Ann Rheum Dis 2011 [2]G Valentini et al. Clin Exp Med 2017 [3]Manetti M, et al. Ann Rheum Dis 2010 [4]Terras S et al. Ann Rheum Dis 2013 [5]Vettori S, et al. J Clin Immunol 2014 Disclosure of Interests: None declared