{
  "abstract": "Background In the American College of Rheumatology/European Alliance of Rheumatology Associations 2010 classification criteria for rheumatoid arthritis (RA), rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are assigned the same weight, although ACPA have proven more specific than RF. We aimed to refine the serological weight factors for RA classification.Materials and methods Diagnostic samples from 398 patients with RA and 448 diseased controls (DC) were evaluated with RF and ACPA assays from five different manufacturers. A grid search was conducted across all possible integer score pairs for RF and ACPA to identify the weighting combination that optimised the specificity of RA classification. This combination was applied in a refined scoring system (RSS) for three confirmatory cohorts comprising, respectively, 67, 157 and 132 patients with RA and 441, 153 and 193 DC.Findings In the investigative cohort, the optimal combination of weighting scores was characterised by higher scores for ACPA, higher antibody levels and double RF/ACPA positivity.Applying the optimal combination of weighting scores decreased misclassification compared with the 2010 RA classification criteria, minimally affecting sensitivity. For seropositive patients, RSS significantly lowered misclassification from 38.3–55.8% to 15.0–26.9%.The improved specificity of RSS (compared with the 2010 criteria) was validated in the confirmatory cohorts. Considering only seropositive patients, the RSS significantly decreased RA misclassification (8.6–36.8% vs 20.0–78.9%), minimally affecting the sensitivity (86.7–97.3% vs 86.7–96.0%).Interpretation Serological weight factors for RA classification can be improved by taking into account the antibody type, the antibody levels and single or combined positivity. The application of an RSS reduced the number of RA misclassifications.",
  "authors": [
    {
      "affiliations": [
        "Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium",
        "Department of Laboratory Medicine, AZORG Hospital, Aalst, Belgium"
      ],
      "name": "Lieve Van Hoovels"
    },
    {
      "affiliations": [
        "Department of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium"
      ],
      "name": "Chatzichristos Christos"
    },
    {
      "affiliations": [
        "Immunopathology Group, Department of Immunology, Marqués de Valdecilla University Hospital-IDIVAL, Santander, Spain"
      ],
      "name": "Irure-Ventura Juan"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium"
      ],
      "name": "Vandebeek Daphné"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium"
      ],
      "name": "Lodewijckx Elke"
    },
    {
      "affiliations": [
        "Department of Rheumatology, AZORG, Aalst, Belgium"
      ],
      "name": "Vander Cruyssen Bert"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"
      ],
      "name": "Sieghart Daniela"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Ghent University, Gent, Belgium",
        "Department of Diagnostic Sciences, Ghent University, Gent, Belgium"
      ],
      "name": "Bonroy Carolien"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary"
      ],
      "name": "Nagy Eszter"
    },
    {
      "affiliations": [
        "Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital Gothenburg, Gothenburg, Sweden",
        "Department of Rheumatology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Pullerits Rille"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia",
        "Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Čučnik Saša"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Dahle Charlotte"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Heijnen Ingmar"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland"
      ],
      "name": "Bernasconi Luca"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg"
      ],
      "name": "Benkhadra Farid"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, AZORG Hospital, Aalst, Belgium"
      ],
      "name": "Bogaert Laura"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, AZORG Hospital, Aalst, Belgium"
      ],
      "name": "Van Den Bremt Stefanie"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, AZ Sint-Elisabeth, Zottegem, Belgium"
      ],
      "name": "Van Liedekerke Ann"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, AZ Rivierenland, Bornem, Belgium"
      ],
      "name": "Vanheule Geert"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine, AZ Sint-Lucas, Bruges, Belgium"
      ],
      "name": "Robbrecht Johan"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg"
      ],
      "name": "Wirth Claudine"
    },
    {
      "affiliations": [
        "Rheumazentrum Ostschweiz, St.Gallen, Switzerland"
      ],
      "name": "Müller Rüdiger"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Kyburz Diego"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Sjöwall Christopher"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Kastbom Alf"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Ješe Rok"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"
      ],
      "name": "Jovancevic Boja"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary"
      ],
      "name": "Kiss Emese"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Ghent and VIB Inflammation Research Center, Ghent, Belgium"
      ],
      "name": "Jacques Peggy"
    },
    {
      "affiliations": [
        "Department of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium",
        "Department of Development and Regeneration KU Leuven, University Hospital Leuven, Leuven, Belgium"
      ],
      "name": "De Vos Maarten"
    },
    {
      "affiliations": [
        "Immunopathology Group, Department of Immunology, Marqués de Valdecilla University Hospital-IDIVAL, Santander, Spain",
        "Department of Molecular Biology, University of Cantabria, Cantabria, Spain"
      ],
      "name": "López-Hoyos Marcos"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria",
        "Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria"
      ],
      "name": "Steiner Günter"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium",
        "Department of Development and Regeneration KU Leuven, University Hospital Leuven, Leuven, Belgium"
      ],
      "name": "Verschueren Patrick"
    },
    {
      "affiliations": [
        "Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium",
        "Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium"
      ],
      "name": "Bossuyt Xavier"
    }
  ],
  "title": "Refining serological scores in rheumatoid arthritis classification: an international study",
  "uid": "31ee8729-27d9-5331-becc-bbe3c08f4f83"
}