{
  "abstract": "Introduction Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15), a pro-fibrotic and pro-inflammatory cytokine, has been implicated in inflammatory bowel disease and intestinal fibrosis. Experimental evidence implicates TL1A-mediated interactions also in interstitial lung disease (ILD), while a neutralizing antibody against TL1A is in phase-2 clinical trial for SSc-ILD. Herein, we examined the potential prognostic value of circulating TL1A and its decoy receptor-3 (DcR3) levels in SSc.Material and Methods Ninety-three consecutive, unselected patients with variable SSc duration, severity and treatment modalities were included. Fifty-four individuals with primary Raynaud’s phenomenon (RP) and 49 apparently healthy individuals served as controls. Baselines serum TL1A and DcR3 were measured using ELISA. Clinical and capillaroscopy characteristics, pulmonary function tests [including forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity of the lung for carbon monoxide (DLCO)] and treatment modalities were analyzed at baseline and yearly for 2 consecutive years. A receiver operating characteristic curve analysis was used to examine the potential prognostic value of baseline TL1A and DcR3 levels for SSc progression over the next 2 years according to the MINIMISE endpoint for mortality and morbidity.Results Both TL1A and DcR3 serum levels were increased in SSc patients compared to healthy (both p<0.001) and primary RP controls (p=0.053 and p<0.001, respectively). No correlations between circulating TL1A levels and SSc baseline characteristics or progression were revealed. However, when patients were stratified in 3 subgroups according to DcR3 levels, being in the lower DcR3 tertile was associated with lower prevalence of ILD, modified SSc activity index values, and systemic inflammatory markers (ESR, CRP), but higher DLCO, comparing to middle and highest DcR3 tertiles, despite comparable age, sex ratio, disease duration and disease subtype. Moreover, analysis of 41 patients with available 2-year follow-up suggested that baseline DcR3 levels are of prognostic value for disease progression at 24 months (AUC=0.684, p=0.03). In addition, SSc progression over the next 2 years was evident in 11/27 (41%) vs 1/14 (7%) patients in the high vs low DcR3 group (p=0.03). The association of higher DcR3 with disease progression remained significant when controlling for age and sex [OR (95%CI): 9.3 (1.04-83.1), p=0.04].Conclusions Circulating DcR3 levels correlate with SSc severity in unselected patients and may serve as a prognostic marker for disease progression regardless of treatment modalities. Experimental studies and clinical studies in selected patient cohorts to explore the role of DcR3-mediated interactions in SSc are warranted.",
  "authors": [
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Vasiliki Poulia"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Nikolaos I Vlachoyiannis"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Aikaterini Avdi"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Vasiliki-Kalliop Bournia"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Maria G Tektonidou"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Petros P Sfikakis"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece"
      ],
      "name": "Stylianos Panopoulos"
    }
  ],
  "title": "P.091 Circulating levels of TL1A and DCR3 molecules and systemic sclerosis progression",
  "uid": "12f0794c-c65e-5acc-8a2b-a65aa7458df2"
}