{
  "abstract": "Introduction Systemic sclerosis (SSc) is a chronic inflammatory disease of the connective tissue characterized by microvascular damage, skin fibrosis and immune system defects. A possible role in the progression of the disease could be played by circulating molecules able to maintain chronic inflammation. Circulating free mitochondrial DNA (cf-mtDNA) triggers inflammation by acting as a Damage-Associated Molecular Pattern (DAMP) and promoting activation of innate immune cells. Cf-mtDNA is sensed by immune cells via TLR9, inducing the expression of IL-6, TNFa, and IFNa, while cytosolic inflammasome component NLRP3 senses ox-mtDNA and promotes the maturation of IL-1b and IL-18, indicating the involvement of proinflammatory pathways. Circulating mtDNA has been demonstrated to enhance inflammation in several chronic inflammatory diseases, including cardiovascular diseases. Nevertheless, its role has never been explored in SSc, despite a deep involvement of cardiac complications in disease prognosis.The aim of the study was to shed light on the contribution of mtDNA to the onset and maintenance of the chronic proinflammatory state observed in SSc. Specifically, we sought to determine whether, and to what extent, the release of mtDNA in the bloodstream contributes to the inflammatory status observed in patients with SSc.Material and Methods We enrolled 70 patients with SSc (mean age 60 y 14; 63 F, 7 M) along with 67 age- and sex-matched healthy controls. Total DNA was extracted from plasma samples, and a droplet digital PCR assay was used to quantify cf-mtDNA. Monocytes were isolated from a subset of patients and treated with mtDNA alone or in combination with LPS, to evaluate its capability to trigger inflammation.Results Cf-mtdna levels were lower in ssc patients than controls (70 vs 67; p<0.01) ( figure 1A). The differences were preserved after stratification according to sex; a positive correlation was observed with age only in female patients (figure 1B). However, cf-mtDNA alone was able to induce an increase in maximal mitochondrial respiration in SSc patients while no effect has been observed in healthy controls, suggesting that it could exert a pro-inflammatory activity that could contribute to the maintenance of chronic inflammation in SSc (figure 2A-B).Conclusions This study explore for the first time a basic mechanism that could link inflammation, chronic activation of innate immune cells and mtDNA, providing a possible marker for evaluating the natural course of the disease.Abstract P.022 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Martina Orlandi"
    },
    {
      "affiliations": [
        "Department of Life Sciences, University of Modena and Reggio Emilia., Modena, Italy"
      ],
      "name": "Sinigalia Giorgia"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Amelia Spinella"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Marco De Pinto"
    },
    {
      "affiliations": [
        "Department of Life Sciences, University of Modena and Reggio Emilia., Modena, Italy"
      ],
      "name": "Isabella Martuscello"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Giorgia Roveta"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Luca Keller"
    },
    {
      "affiliations": [
        "Department of Life Sciences, University of Modena and Reggio Emilia., Modena, Italy"
      ],
      "name": "Marcello Pinti"
    },
    {
      "affiliations": [
        "Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Dilia Giuggioli"
    }
  ],
  "title": "P.022 Contribution of mitochondrial DNA to the onset and maintenance of inflammation in systemic sclerosis patients",
  "uid": "6717107b-488c-5440-9795-bf34668cfe47"
}