{
  "abstract": "Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, inflammation, and fibrosis. Endothelial dysfunction is an early event, associated with hypoxia, vasoconstriction-vasodilation and angiogenesis imbalance.Platelets, in addition to their role in hemostasis, recruit immune cells and release pro-fibrotic mediators. Recent studies demonstrate increased levels of platelet products in SSc serum, suggesting increased platelet activity, although antiplatelet therapy use is controversial. Comprehensive phenotypic analysis of platelets in SSc remains limited. This preliminary study aims to further investigate platelet functions in patients with SSc and with Very Early Diagnosis of Systemic Sclerosis (VEDOSS).Material and Methods This single-center study enrolled consecutive adult patients diagnosed with SSc according to the ACR/EULAR 2013 criteria or fulfilling VEDOSS criteria, not in antiplatelet therapy. Age- and sex-matched healthy controls (HC) were selected. Blood samples were analyzed within 30 minutes of collection. Platelet activation and reactivity were assessed by staining blood diluted in Tyrode buffer with CD62P-PE and PAC1-FITC, in the absence/presence of agonists (ADP, convulxin, TRAP-6). Mitochondrial function was studied with MitoTracker Green FM and MitoTracker CMXRos on washed platelets, with/without agonists. The analysis was conducted with a BD Accuri C6 Plus flow cytometer and FlowJo™ software and GraphPad Prism software version 10.4.2.Results Twelve SSc patients [median age 60 (37-65), F 100%], 3 VEDOSS patients [age 51 (55-54), F 100%] and 6 HC [age 59 (30-65), F 100%] were enrolled. In SSc, unstimulated platelets are significantly more activated than HC [0,26 (0,03-29) vs 0,02 (0,01-2,2), p<0.05]. Interestingly, platelets from VEDOSS cases showed higher reactivity following stimulation with convulxin than SSc patients [91,8 (90,6-92,8)% vs 80,1 (61,2-90,5)%, p<0.01] and HC [91,8 (90,6-92,8)% vs 80,30 (68,8-86,9)%, p<0.05]. In VEDOSS patients circulating platelets showed significant mitochondrial dysfunction, both unstimulated and after agonist stimuli, when compared to SSc patients and HC.Conclusions Our preliminary data showed different platelet functions and metabolism in VEDOSS patients than in SSc patients, suggesting an interesting role of platelets in the early stage of disease.Of note, in VEDOSS cases platelets were significantly more responsive to convulxin, a strong agonist of platelet activation, mimicking collagen exposure, involved in endothelial dysfunction.Besides in VEDOSS patients, mitochondrial dysfunction suggests elevated platelet activity, confirming the role of platelets in early vascular damage. Further studies on larger and better characterized cohorts of patients with VEDOSS and SSc are needed to elucidate the pathogenetic role of platelets as well as their potential target treatment.Abstract OC.35 Figure 1Mitochondria in HC, SSc, and VEDOSS patientsAbstract OC.35 Figure 2Platelets activation in HC, SSc and VEDOSS patients",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical, Internal Medicine, Anesthesiology, and Cardiovascular Sciences, University of Rome ‘La Sapienza,’ Rome, Italy",
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy",
        "Department of Molecular Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Annalisa Villa"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Marcella Visentini"
    },
    {
      "affiliations": [
        "Department of Clinical, Internal Medicine, Anesthesiology, and Cardiovascular Sciences, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Simona Truglia"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Francesca Maiorca"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Annamaria Sabetta"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Ludovica Lombardi"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Silvia D’orso"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Francesca La Gualana"
    },
    {
      "affiliations": [
        "Department of Clinical, Internal Medicine, Anesthesiology, and Cardiovascular Sciences, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Fabrizio Conti"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Lucia Stefanini"
    },
    {
      "affiliations": [
        "Department of Clinical, Internal Medicine, Anesthesiology, and Cardiovascular Sciences, University of Rome ‘La Sapienza,’ Rome, Italy"
      ],
      "name": "Valeria Riccieri"
    }
  ],
  "title": "OC.35 Platelets’ metabolism and functions in very early diagnosis of systemic sclerosis and in established disease",
  "uid": "114e78de-90e7-53a0-b617-919f02906a28"
}