{
  "abstract": "Objectives Activated synovial fibroblasts play a key role in rheumatoid arthritis (RA). Positron emission tomography-CT (PET-CT) using 68gallium-labelled fibroblast activation protein inhibitor (FAPI) allows the detection of FAP-expressing activated fibroblasts in humans in vivo. Herein, this study aimed to investigate whether fibroblast activation already occurs in the pre-clinical phase of RA and whether it is associated with the development of clinical disease.Methods 68Ga-FAPI-46 PET-CT was performed in individuals positive for anti-citrullinated protein antibodies (ACPAs) with clinically suspect arthralgia without present or past signs of joint swelling or present or past anti-rheumatic therapy. All participants underwent structured clinical and laboratory evaluations and were followed for the development of RA. Synovial FAPI uptake was quantified and related to demographic characteristics, joint tenderness, ACPA levels and RA development.Findings Eighteen RA-at-risk individuals (male/female: 7/11; mean age, 47 (SD 14) years) underwent 68Ga-FAPI-46 PET-CT and were followed for a median of 42 weeks. Five participants (28%) developed RA with a median of 12 weeks (IQR, 11–20), whereas 13 remained disease-free. Total lesion FAPI-uptake (TL-FAPI) was a significant predictor of RA development (HR 4.58, 95% CI 1.38 to 15.22, p=0.013). Increasing TL-FAPI at the joint level was also associated with tenderness (isk ratio 1.14, 95% CI 1.08 to 1.22, p=0.001).Conclusions The findings in this small RA-at-risk cohort suggest that synovial fibroblast activation occurs early in the disease process of RA and is associated with an increased risk for clinical RA onset. These results warrant further research on FAPI-PET-CT to improve risk assessment for clinical RA onset.",
  "authors": [
    {
      "affiliations": [
        "Department of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Armin Atzinger"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Koray Tascilar"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology, Charite - Universitatsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Arnd Kleyer"
    },
    {
      "affiliations": [
        "Paracelsus Medical Private University Institute of Physiology Pathophysiology and Biophysics, Nuremberg, Germany"
      ],
      "name": "Axel J Hueber"
    },
    {
      "affiliations": [
        "Institute for Medical Engineering, Ostbayerische Technische Hochschule Amberg-Weiden, Amberg, Germany"
      ],
      "name": "Christian Schmidkonz"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Torsten Kuwert"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Michael Beck"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Filippo Fagni"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Giulia Corte"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Andreas Ramming"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Georg Schett"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany"
      ],
      "name": "Sara Bayat"
    }
  ],
  "title": "Synovial fibroblast activation occurs before the onset of rheumatoid arthritis and influences the risk of developing disease",
  "uid": "0b4afc53-525b-5254-8f64-999a4567336d"
}