{
  "abstract": "Introduction SSc is a autoimmune disease characterised by vascular changes and fibrosis of the skin and visceral organs.Although the pathogenesis of SSc is poorly understood,immunological,vascular and extracellular matrix protein abnormalities seem to play an essential role in the disease process.Vascular damage resulting in endothelial cell injury,cytokine and adhesion molecule synthesis,followed by fibroblast activation and excessive tissue matrix protein production play a central role in the SSc-pathogenesis.The main effector cells,the myofibroblasts,are collagen-producing cells derived from the activation of resting fibroblasts.This process is regulated by a complex repertoire of profibrotic cytokines,and among them TGF-B and ET-1 play a major role.VEGF,as a fundamental modulator of angiogenesis,is involved in the pathogenesis of SSc.Since the clinical course of SSC in an individual patient is unpredictable,rheumatologists would benefit from tests to identify patients who may develop ILD,which is the main cause of death in SSc.These biomarkers have been reported to correlate with poor clinical outcome.Objective To find out whether the levels of VEGF,ET-1,TGF-B are associated with the development and progression of SSc-ILD.Material and Methods 66 patients with SSc-ILD were enrolled into the study(disease duration-7.2±5.6 years,diffused/limited-1.7/1,average age-50.3±12.6 years,females-77%).All patients received glucocorticoids(GC) and immunosuppressants(IS),45(68%)-rituximab(RTM) at cumulative dose 2.4±1.5 grams.The level of TGF-B,ET-1,VEGF was determined by the ELISA method.Subsequently correlation analysis was made to clarify the association of studied biomarkers with the main clinical manifestations,activity of SSc,laboratory parameters(ESR,CRP,ANA-HEP-2,a-Scl-70,B-cell-count),GC and IS-therapy and cumulative RTM-dose.Results When studying the association of biomarkers with radiological symptoms of ILD,a direct correlation of ET-1,TGF-B,VEGF levels with the presence of ‘ground glass’ was obtained(r=0.38;0.309;0.327,respectively).ET-1 levels were inversely correlated with DLCO(r=-0.4) and the 6-MWT.The analysis of laboratory inflammatory activity indicators revealed a direct correlation of ESR with TGF-B(r=0.309).No influence has been established of IS on the level of any markers.An inverse correlation of the GC-dose with TGF-B(r=-0.544),VEGF(r=-0.38) was revealed.The level of ET-1 was inversely correlated with the duration of GC-therapy(r=-0.34).A large total dose of RTM was associated with a decrease in ET-1 levels.Conclusions The detection of increased levels of TGF-B,VEGF,and ET-1 in patients with SSc may serve as a basis for a more in-depth diagnostic search to identify the ILD.The identification of the lowest DLCO values in patients with elevated ET-1 levels allows us to consider ET-1,as a predictor of deterioration of pulmonary function.A decrease in ET-1 levels during a-B cell-therapy may indicate the potential role of this biomarker in evaluating the effectiveness of therapy.",
  "authors": [
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Olga Koneva"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Rushana Shayachmetova"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Liudmila Garzanova"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Anastasia Avdeeva"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Michail Diatroptov"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Olga Ovsyannikova"
    },
    {
      "affiliations": [
        "V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia"
      ],
      "name": "Lidia Ananyeva"
    }
  ],
  "title": "P.102 Association of interstitial lung disease (ILD) with markers of microvascular damage and fibrogenesis in systemic sclerosis (SSc",
  "uid": "e09e08db-0a46-560c-9ab4-388a66f8a39b"
}