{
  "abstract": "Objectives We aimed to identify biomarkers with capacity to predict damage accrual over the first 5 years of SLE, and to compare the predictive capacity with soluble urokinase plasminogen activator receptor (suPAR), a protein previously demonstrated to predict organ damage development in the SLICC cohort.Methods Sera from 274 newly diagnosed Swedish patients were analysed for 184 proteins by proximity extension assay (Olink® panels: Inflammation and Organ Damage) and suPAR (ELISA). Organ damage was assessed by the SLICC/ACR Damage Index (SDI). Proteins which were significantly associated with organ damage at the 3- or 5 years of follow up (unadjusted analysis, any of two different cut-offs) were further explored regarding protein interactions using String v. 12.0. In addition, associations with SDI were adjusted for: 1) disease activity (SLEDAI-2K); 2) eGFR in a logistic regression (forward conditional). Proteins still associated with SDI after adjustment were further adjusted for age, and corticosteroids (binary), and thereafter explored by adding suPAR to the regression model.Results 33 proteins were associated with organ damage development and were clustered in three groups ( figure 1). Of these proteins, 6 remained associated with SDI at 3 and 5 years (any cut-off) after adjustment for SLEDAI, eGFR, age and corticosteroids. These proteins were found in the viral protein signaling cluster (IL-18R1; IL-18 receptor 1, NOS3; nitric oxide synthase 3, PD-L1; Programmed death-ligand 1) and the protein deacetylase activity cluster (SIRT2; Sirtuin 2) as well as non-clustered proteins; DSG4 (desmoglein 4, expressed in the skin) and CDCP1 (CUB Domain Containing Protein 1, associated with cancer). Addition of suPAR to the models revealed that the Olink proteins were better associated with organ damage (SDI>0) after 3 years and 5 years, whereas suPAR was better associated with organ damage at the higher cut-off (SDI>1), 3 years after diagnosis.Abstract PO:02:056 Figure 1Volcanoplots showing differences in protein levels (NPX) measured at diagnosis, depending on organ damage (SDI) status after 3 and 5 years (unadjusted t-test). Top ten proteins (uniprot names) are labeled. Two cut-offs were applied for SDI (upper and lower panel). Proteins with significant differences at 3 and 5 years (any cut-off) are listed in the first column to the right (n=33) and proteins that remained associated with SDI after statistical adjustments are shown in the following columns. The 33 proteins were explored for protein interactions using String v. 12.0. VEGFA was not found in the database and was replaced by its receptor VEGFR2. Three clusters were created and described as follows: Red cluster: Viral protein interaction with cytokine and cytokine receptor/Interleukin-10 signaling Green cluster: Vascular endothelial growth factor signaling pathway. Blue cluster: Nicotinate and nicotinamide metabolism/NAD-dependent protein deacetylase activityConclusions DSG3, SIRT2 and CDCP1 have been scarcely investigated in SLE and show promise for prediction of organ damage in SLE. Furthermore, we demonstrate a predictive capacity of proteins in the viral pathway which may indicate an important role of high disease activity in early organ damage development. Associations between proteins and specific damage types will be analysed next.",
  "authors": [
    {
      "affiliations": [
        "Linköping University – Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Helena Enocsson"
    },
    {
      "affiliations": [
        "Lund University and Skåne University Hospital – Department of Clinical Sciences, Lund, Sweden"
      ],
      "name": "Andreas Jönsen"
    },
    {
      "affiliations": [
        "Uppsala University – Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Maija-Leena Eloranta"
    },
    {
      "affiliations": [
        "Lund University and Skåne University Hospital – Department of Clinical Sciences, Lund, Sweden"
      ],
      "name": "Birgitta Gullstrand"
    },
    {
      "affiliations": [
        "Uppsala University – Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Nina Oparina"
    },
    {
      "affiliations": [
        "Lund University and Skåne University Hospital – Department of Clinical Sciences, Lund, Sweden"
      ],
      "name": "Anders A Bengtsson"
    },
    {
      "affiliations": [
        "Karolinska Institute – Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Karolinska Institute – Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Elisabet Svenungsson"
    },
    {
      "affiliations": [
        "Uppsala University – Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Lars Rönnblom"
    },
    {
      "affiliations": [
        "Uppsala University – Department of Medical Sciences, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    },
    {
      "affiliations": [
        "Linköping University – Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Christopher Sjöwall"
    }
  ],
  "title": "PO:02:056 Prediction of future organ damage in recent onset SLE by serum proteomics",
  "uid": "0525219b-99a3-5849-b4db-4264a525737d"
}