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Background Endothelial-to-mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation, seems to be involved in Systemic Sclerosis (SSc) pathogenesis. In this process endothelial cells lose their specific markers, and acquire a mesenchymal phenotype, thus expressing cell products such as alpha smooth muscle actin (α-SMA) (1,2). Circulating endothelial progenitors cells (EPCs) derive from bone marrow stem cells and contribute to de novo vessels formation. Several studies, although with conflicting results, have shown that EPCs in the peripheral blood of patients with SSc are impaired in their number and function (3). Objectives to assess the expression of α-SMA, possibly associated with a pro-mesenchymal switch (EndoMT) of the circulating Early (CD34+KDR+CD 133+) and Late (CD34+KDR+) EPCs in the peripheral blood of SSc patients and of patients with Very Early Diagnosis of SSc (VEDOSS) compared with healthy controls (HC) using flow cytometry. Methods we enrolled 11 patients (7 SSc and 4 VEDOSS), classified according to the classification criteria for SSc (4) and for VEDOSS not fulfilling SSc criteria (5), and 10 HC. Phenotypic characterization was performed as previously described by Vasa et al. using a FACS Calibur (BD Immunocytometry Systems). EPCs number was expressed as a percentage of cells within the lymphocyte gate. Results we found a significantly higher percentage of α-SMA positive Early EPCs (CD34+KDR+CD 133+αSMA+) in all patients respect to HC (0,06% ±0,03 vs 0,03% ± 0,01; p=0,0149) particularly in VEDOSS patients (0,07%±0,01 vs 0,03±0,01 p=0,008). Moreover, in VEDOSS patients, also the percentage of Early EPCs (CD34+KDR+CD 133+), Late EPCs (CD34+KDR+)and α-SMA positive Late EPCs (CD34+KDR+αSMA+) were significantly higher than in HC (0,05%±0,01 vs 0,03%±0,01 p=0,05; 0,07%±0,01 vs 0,04%±002 p=0,04; 0,06%±0,01 vs 0,04%±0,02 p=0,05). Besides Early EPCs and α-SMA positive Early EPCs percentages seem to be significantly reduced in patients taking iloprost (p=0,05 and p=0,01 respectively), calcium channel blockers (CCB) (p=0,05 and p=0,03) and DMARDs (p=0,017 and p=0,013). Conclusion EndoMT seems to be involved in the pathogenesis of SSc and circulating EPCs seem to be impaired in number and function in SSc patients. In our study we found higher levels of EPCs, in particular α-SMA positive Early EPCs in both groups of patients (SSc and VEDOSS) respect to HC. Thus we can hypothesize a predominant pro-mesenchymal phenotype of this kind of EPCs. This could be considered the expression of the involvement of EPCs in EndoMT process and could better explain the controversial role of EPCs in SSc pathogenesis. Very interesting is the finding of a lower percentage of Early EPCs, and in particular of α-SMA positive Early EPCs, in those patients taking iloprost, CCB and DMARDs, suggesting a potential effect of these drugs on this subgroup of EPCs. References [1] Corallo C, et al. Arthritis Res Ther2016; [2] Manetti M, et al. Ann Rheum Dis2017; [3] Del Papa N, et al. Front. Immunol2018; [4] Van den Hoogen F, et al. Ann Rheum Dis2013; [5] Avouac J, et al. Ann Rheum Dis2011. Disclosure of Interests Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, cristiana barbati: None declared, Carlotta Angelelli: None declared, Greta Pellegrino: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared

Background: an increased risk of malignancies (1.5-5 times) was found in Systemic Sclerosis (SSc). Well recognized risk factors are the diffuse form, advanced age and (1), more recently, the positivity for anti-RNA Polimerase III antibodies (aRNAP3) has assumed considerable importance (2). Objectives: the aim of this study was to evaluate the frequency of neoplasms and precancerous conditions, as well as the main risk factors, in our cohort of patients with SSc. Methods: we enrolled 312 consecutive patients (288/92% females and 24/8% males, mean age 62.3 years, average disease duration 108 months) afferent at our department from 2000 to 2018, with a diagnosis of SSc confirmed according to the 2013 aCR/EULAR criteria (3). All patients underwent clinical, instrumental and laboratory evaluation. In 93 patients, negative for anti-topoisomerase I antibodies (aScl70) and anti-centromere antibodies (ACA), the presence of aRNAP3 antibodies was evaluated by an ELISA method (QUANTA LiteTM RNA Pol III). Results: we found a limited form of disease in 229 patients (73.4%) and a diffuse form in 83 (26.6%). Eighty eight (28.2%) patients were positive for aScl70, 112 (35.9%) for aCA and 17 (5.4%) for aRNAP3. In the whole group, 44 (14%) patients had a positive familiar history for neoplasm while 105 (33.65%) had a history of neoplasms and/or precancerous conditions. Among these 105 cases, 44 (41.9%) were malignant, 50 (47.6%) benign and 11 (10.5%) had precancerous conditions. The most frequent neoplasms were breast carcinomas (14 cases/14.9%), thyroid (7 cases/7.4%), lung and kidney (3 cases/3.1%), melanomas (5 cases/5.3%). The most frequent precancerous condition was Barrett’s esophagus (7 cases/63.3%). Regarding the antibody profile, 5 (4.8%) patients were positive for anti-RNAP3 and only 2 (1.9%) of these patients presented a malignant neoplasm, breast cancer in both cases. In 30 cases (28.6%) these neoplastic/precancerous conditions had arisen in the close period (± 36 months) at the SSc diagnosis and only 3 of them were anti-RNAP3 positive. Among the evaluated risk factors. Only familiarity was significantly associated with the development of neoplasia (p = 0.003), confirmed at the multivariate analysis (OR 2.9, IC95% [1,5-5,7]; p=0,002). Conclusion: our study evaluated not only malignant neoplasms, but also benign neoplasms and precancerous conditions and identified familiarity as the only significant risk factor. In our cohort we did’nt find any relationship between the presence of anti-RNAP3 antibodies and the development of neoplasms, not even stratifying for the type of neoplasm. However, to better define our data, we should analyze anti-RNAP3 also in the double negative (antiScl70 and aCA) cases, in light of the recent evidence of double antibody positivity, as well as other newly investigated rare autoantibodies, associated with neoplasm in many connective tissue diseases, including SSc. References [1] Szekanecz E, et al. (2012) autoimmun Rev11, 852; [2] Shaha aAet al(2017) J Scleroderma Relat Disord. 2, 153; [3] Van den Hoogen F, et al. (2013) ann Rheum Dis72, 1747–55. Disclosure of interests: Katia Stefanantoni Consultant for: only 1 scientific advice for Italfarmaco in 2016, Natalia Di Tommaso: None declared, Nicoletta Iannace: None declared, Iliana Sciarra: None declared, Carlotta angelelli: None declared, Elena Marafioti: None declared, Greta Pellegrino: None declared, massimiliano vasile: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared