ROLE OF IL-33/ST2 AXIS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

BackgroundElectrocardiographic (EKG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) patients and they are associated with other systemic manifestations1 as well as with a worse prognosis.2 There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic approaches to patients with EKG abnormalities.3In the last decade, many studies focused on the components of the interleukin (IL)-33/ST2 axis. Under physiological conditions, IL-33 is released by apoptotic cardiac cells, promoting a protective mechanism of cell survival, thanks to the binding with its transmembrane receptor ST2.4 During pathological cardiovascular events, an abnormal secretion of the IL-33 soluble receptor (sST2) by Th2 cells occurs. It binds IL-33 not allowing the physiological mechanism driven by the IL-33/ST2 binding previously described.4 For these reasons, sST2 has been proposed as a biomarker of cardiac injury in a variety of diseases.5ObjectivesAim of this study was to analyse clinical and demographical parameters in a group of SSc patients, trying to define any possible feature associated with EKG abnormalities. Furthermore, the role of IL-33/ST2 axis components as biomarkers of cardiac injury in patients with SSc-related EKG abnormalities was evaluated, also assessing the possible correlation with serum concentration of NT-pro-BNP, a well-known cardiac injury biomarker in SSc.MethodsData from 277 SSc patients, fulfilling the 2013 ACR/EULAR classification criteria,6 attending our Scleroderma Clinic were retrospectively analysed. We selected patients with EKG trace and a blood sample available, collected after the SSc diagnosis. The sera levels of sST2 (ELISA Kit, Abcam), IL-33 (ELISA kit, RayBiotech) and NT-pro-BNP (ELISA Kit, Abcam) were measured. Patients with a history of heart diseases occurring before the diagnosis of SSc or features of secondary cardiac involvement (pulmonary arterial hypertension, severe interstitial lung disease or renal disease) were excluded.ResultsForty-six SSc patients showed significant EKG abnormalities (rhythm and conduction disorders). Thirty-one SSc patients without pathologic finding at EKG traces were recruited as the control group.From the analysis of the clinical characteristic of the disease at the moment of serum collection, patients with EKG anomalies have more frequently both a diffuse form of disease (n°-%: 23-50 vs 7-23; p 0.01), with a mean value of mRSS higher than controls (11±9 vs 6±6; p 0.01), and a scleroderma “late” pattern at the nailfold capillaroscopy (n°-% 23-50 vs 6-19; p 0.027).Significantly higher median values of serum levels of sST2 in SSc patients with EKG disorders compared to the control group (4289pg/mL, IQR 2383 vs 2560 pg/mL, IQR 1455; p 0.0002) were detected, while opposite results were found analyzing serum levels of IL-33 (2.89 pg/mL IQR 101 vs 9 pg/mL IQR 277; p 0.032) (Graph 1). Serum NT-pro-BNP median values were significantly higher in the group of patients with EKG abnormalities than in the control group (149 pg/mL, IQR 354 vs 26 pg/mL, IQR 62; p 0.0007). These values correlated with sST2 serum levels (rho Spearman correlation 0.37; p 0.0006).ConclusionSSc patients with EKG abnormalities showed an increased skin and vascular involvement with respect to the control group. These associations could help clinicians in clinically stratifying SSc patients at risk of EKG abnormalities. To our knowledge, this is the first report evaluating the serum concentration of sST2 in SSc patients. Based on these results, we can speculate on the role of this molecule as potential biomarkers of early cardiac injury during SSc, although further studies involving a larger cohort of patients are needed.References[1]Vacca et al. Rheumatol 2014[2]Tyndall et al. Ann Rheum Dis 2010[3]Muresan et al. Clin Rheumatol 2018[4]Vianello et al. Int J Biochem Cell Biol 2019[5]Dudek et al. Adv Clin Exp Med 2020[6]van den Hoogen et al. Arthritis Rheum 2013Figure 1:Graph 1. Serum sST2 (a) and IL-33 (b) concentrations in patients with EKG abnormalities (EKG+) vs control group (EKG)Disclosure of InterestsNone declared.