Op0246 predictive Value of Laboratory and Instrumental Findings in the Very Early Diagnosis of Systemic Sclerosis. Role for Cxcl4 Chemokine

Abstract

Background:Systemic sclerosis (SSc) is a rare and progressive autoimmune disease, whose diagnosis is difficult in the early stages because of the lack of specific signs and symptoms. Criteria for a Very Early Diagnosis of SSc (VEDOSS) have been proposed to identify those patients affected by undifferentiated connective tissue disease (UCTD) at risk to develop SSc [1]. For the diagnosis of SSc a strict clinical and laboratory follow up is mandatory [2]. CXCL4 chemokine recently proved to be higher in early SSc [3][4][5].Objectives:Aim of our study was to evaluate at baseline the main clinical-demographic and laboratory parameters in a group of VEDOSS patients, comparing these features during the follow-up, to detect any difference between progressors (P) and non-progressors (NP) into SSc. Furthermore, we dosed plasma levels of CXCL4.Methods:We included 27 VEDOSS patients, defined by EUSTAR 2011 Criteria and not fulfilling the 2013 ACR/EULAR classification criteria of SSc, attending the Rheumatology Unit of Policlinico Umberto I in Rome from 2009 to 2020. Demographic, laboratory and instrumental features were analyzed, and, after a mean follow-up of 5.7±1,7 years, we compared the P to NP patients. Having obtained written informed consent, blood samples were taken at baseline to measure plasma levels of CXCL4 chemokine using an ELISA assay.Results:At baseline the 27 VEDOSS patients (mean age 53.2±13.5 years, all females) had ANA positivity in 25 (93%) cases and Raynaud’s phenomenon in 25 (93%) cases. In a mean follow-up time of 43.5 ± 23.1 weeks from the first clinical examination, 15 (55%) patients were classified as P into SSc. These P patients showed a significant association with SSc specific antibodies such as anti-Centromere, anti-Scl70 and anti-RNAPIII (p=0.014) as well as with a specific “Scleroderma pattern” at the nailfold capillaroscopy (p=0.022) respect to those NP into SSc. A group of 6 P patients evolved in less than 24 months (mean 19,6 ± 6,8 weeks) and were defined “Fast Progressor”. They were also significantly associated with those autoantibodies considered as having a worse prognosis such as anti-Scl70 and anti-RNAPIII (p=0.005), and had a shorter duration of RP (88 vs 189.3 months) and a younger mean age (49.5 vs 55.4 years) respect to “Slow Progressor” (SSc evolving in >24 months). At baseline we detected significantly higher median plasma levels of CXCL4 in the 27 VEDOSS patients compared to 10 healthy subjects (9024±10559 pg/ml versus 348,5±684,3 pg/ml; p=0.0047). We also noticed a trend for lower CXCL4 levels in the “Fast Progressor” than in the “Slow Progressor” (3303 ± 6065 pg/ml vs 13300 ± 10308 pg/ml; p=0.052) without reaching a significant value, due probably to the low number of cases.Conclusion:Our study confirms that the presence of specific autoantibodies and capillaroscopic abnormalities correlate to an increased risk of developing SSc in patients with UCTD [6]. Beside we found significantly higher levels of CXCL4 in our 27 VEDOSS patients respect to controls, in agreement with other authors showing the association of this chemokine with early stages and specific organ involvement [4][5][7]. The finding of CXCL4 lower levels in “fast progressor” cases is consistent with our recent report of anti-CXCL4 antibodies in patients with early SSc, determining lower levels of this antigen [7]. We need deeper investigations to better evaluate the role of CXCL4 in the different stages of SSc.References:[1]J. Avouac et al., Ann. Rheum. Dis., 2011.[2]F. van den Hoogen et al., Ann. Rheum. Dis., 2013.[3]G. Valentini et al., Clin. Exp. Med., 2017.[4]R. Lande et al., Nat. Commun., 2019.[5]L. van Bon et al., N. Engl. J. Med., 2014.[6]M. Vasile et al., Clin. Exp. Rheumatol., 2018.[7]R. Lande et al., Int. J. Mol. Sci., 2020.Disclosure of Interests:None declared

Op0247 in Myositis Muscle Fibre Plays a Direct and Critical Role in Therapeutic Response to Glucocorticoids

“…Beside we found significantly higher levels of CXCL4 in our 27 VEDOSS patients respect to controls, in agreement with other authors showing the association of this chemokine with early stages and specific organ involvement [4][5][7]. The finding of CXCL4 lower levels in "fast progressor" cases is consistent with our recent report of anti-CXCL4 antibodies in patients with early SSc, determining lower levels of this antigen [7]. We need deeper investigations to better evaluate the role of CXCL4 in the different stages of SSc.…”