{
  "abstract": "Introduction Microangiopathy is an early hallmark of systemic sclerosis (SSc), most frequently represented by peripheral microangiopathy with Raynaud’s phenomenon (RP) and development of digital ulcers (DUs). Vascular damage can involve also kidney with subclinical scleroderma vasculopathy or pulmonary vasculopathy. Autoimmunity is another early feature of SSc; specific autoantibodies, such as anti-centromere (ACA) and anti-topoisomerase I, known as anti-Scl70 (Scl70) antibodies, are central for diagnosis but these antibodies are mostly considered an epiphenomenon of immune cells activation. Nevertheless, some studies have suggested a potential pathogenic role of the humoral response in both the development of the fibrotic phenotype and microvascular damage in SSc. In recent years, functional antibodies directed against endothelial targets, such as endothelin and angiotensin receptor, have been described in SSc. Antibodies against the Angiotensin II type 1 (anti-AT1R) and autoantibodies against endothelin receptor type A (anti-ETAR) have an agonist function on their receptors, amplifying the vasoconstrictive capacity of endothelin and angiotensin are able to induce multiple activating pathway associated to endothelial dysfunction and vascular remodelling.Aims of this study were to evaluate the serum level of anti-AT1R and anti-ETAR in SSc patients and healthy controls (HC) and to evaluate the associations of serum level of these antibodies with microvascular complication of SSc, such as DUs, subclinical renal vasculopathy and early pulmonary vasculopathy.Material and Methods This monocentric observational study enrolled 64 consecutive SSc patients, who met the 2013 ACR/EULAR classification criteria, and 20 HC, matched for sex and age, who were tested for anti-AT1R and anti-ETAR.Results SSc patients had higher anti-AT1R [7.78 ng/ml (IQR 6.14;12.16) vs 3.25 ng/ml (IQR 2.60;4.70), p<0.001] and anti-ETAR [0.16 OD (IQR 0.14;0.17) vs 0.10 OD (IQR 0.10;0.12), p<0.001] than HC. SSc patients with DUs had higher anti-AT1R [10.79 ng/ml (IQR 7.32;14.15) vs 6.76 ng/ml (IQR 5.88;7.88), p<0.001] and anti-ETAR [0.16 OD (IQR 0.15;0.18) vs 0.15 OD (IQR 0.13;0.16), p<0.01] than SSc patients without DUs. We found a positive correlation between renal resistive index (RRI) and anti-AT1R (r=0.357, p<0.01) or anti-ETAR (r=0.442, p<0.001) and a negative correlation between tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/sPAP) and anti-AT1R (r = - 0.436, p<0.001) or anti-ETAR (r = - 0.334, p<0.01).Conclusions Anti-AT1R and anti-ETAR are promising markers of vascular damage in SSc, with implications for patients’ stratification. These antibodies indicate uncontrolled activation of vasoconstrictive systems and may play a pathogenic role in endothelial dysfunction responsible for vasculopathy in SSc.",
  "authors": [
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Chiara Pellicano"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Annalisa Villa"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Giancarlo D’ippolito"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Gabriella Cusa"
    },
    {
      "affiliations": [
        "UOC of Clinical Pathology DEA II level, Hospital Santa Maria Goretti-ASL Latina, Latina, Italia"
      ],
      "name": "Valeria Carnazzo"
    },
    {
      "affiliations": [
        "UOC of Clinical Pathology DEA II level, Hospital Santa Maria Goretti-ASL Latina, Latina, Italia"
      ],
      "name": "Federica Laterza"
    },
    {
      "affiliations": [
        "UOC of Clinical Pathology DEA II level, Hospital Santa Maria Goretti-ASL Latina, Latina, Italia"
      ],
      "name": "Umberto Basile"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Antonietta Gigante"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Roma, Italia"
      ],
      "name": "Edoardo Rosato"
    }
  ],
  "title": "P.067 Anti-endothelial cell antibodies as biomarkers of endothelial dysfunction in systemic sclerosis (SSC) patients",
  "uid": "a5c1d3db-6951-58ef-9eaf-15bd795aa313"
}