{
  "abstract": "Introduction Skin fibrosis is a cardinal manifestation of systemic sclerosis (SSc) and is routinely measured by modified Rodnan skin score (mRSS), which is however is limited by its operator-dependence and may not reflect the complex disease biology at the cutaneous compartment. A recent high dimensional multi-omic analysis identified 3 serum proteins independently associated with mRSS: tenascin C (TNC), cartilage oligomeric matrix protein (COMP), and collagen type IV alpha 1 (COL4A1). The aim of our study was to evaluate the relationship between the serum concentration of the analytes as cross-sectional and dynamic biomarkers for skin involvement in this cohort, as well as to capture potential correlations with type of immunosuppressive treatment.Material and Methods We selected 21 patients from 2 Dutch centres who participated in the Autologous Stem Cell Transplantation International Scleroderma trial - a phase 3, multicentre, randomized study comparing autologous stem cell transplantation (HSCT) to cyclophosphamide (CYC) in diffuse cutaneous (dc)SSc. Serum concentrations of the three analytes were measured with ELISAs at baseline, 12 and 24 months. We employed linear mixed-effects models to assess cross-sectional correlation between mRSS, target analyte concentrations and time, including their fixed effects. We used univariable linear regression to visualize cross-sectional correlation between target analyte and mRSS. A multivariable linear regression model (independent of time) was used to formulate a composite biomarker score to predict mRSS, and Bland Altman plot to determine the agreement between predicted and actual mRSS.Results There were 11 patients in the CYC arm, and 10 to the HSCT arm. Univariable linear regressions of mRSS and target analytes’ concentration are depicted in figure 1. Serum concentrations of COMP and COL4A1, but not TENC, showed significant correlation with mRSS at the mixed model, with COL4A1 maintaining statistical significance at multivariable analysis (β=0.01, p=0.001). We derived a composite serum biomarker formula score to predict mRSS with good performance at Bland Altman plot (figure 2). As dynamic biomarkers, only changes in concentrations of COMP were associated with mRSS change (r= 0.013; p= 0.012). It is notable that there was greater reduction in COL4A1 concentration at 24 months in the HSCT group compared with CYC (-81 ng/mL vs -27.4 ng/mL in CYC group; p= 0.029; figure 3).Conclusions Our composite biomarker score showed good cross-sectional correlation with mRSS score, however not to such an extent to be envisioned as a surrogate of mRSS. The differential variations for serum COL4A1 across treatment groups warrant further evaluation as a predictive marker in dcSSc.Abstract P.228 Figure 1Abstract P.228 Figure 2Abstract P.228 Figure 3",
  "authors": [
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Stefano Rodolfi"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Kristina Klark"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Bahja Ahmed Abdi"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Elen Roblin"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Medha Kanitkar"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Voon H Ong"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centre, Amsterdam, The Netherlands"
      ],
      "name": "Alexandre E Voskuyl"
    },
    {
      "affiliations": [
        "Leiden University Medical Centre, Leiden, The Netherlands"
      ],
      "name": "Jeska K De Vries-Bouwstr"
    },
    {
      "affiliations": [
        "University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Jacob M van Laar"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Christopher P Denton"
    },
    {
      "affiliations": [
        "University College London, London, UK",
        "University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Julia Spierings"
    }
  ],
  "title": "P.228 Formulation of a composite biomarker score to predict modified rodnan skin score: insight from autologous stem cell transplantation international scleroderma trial",
  "uid": "da2050ce-1370-5a52-b067-e643ab102220"
}