{
  "abstract": "Background The aim of this systematic review and meta-analysis was to examine autoantibody positive individuals and define: (a) the relative risk of rheumatoid arthritis (RA) compared with autoantibody negative individuals and (b) the cumulative incidence of RA over time, in different populations.Methods A systematic literature search was performed in August 2025. Retrospective case control studies of individuals with RA and healthy matched controls were identified and relative risk of RA was calculated. Prospective observational studies or randomised controlled trials of autoantibody positive individuals were identified and pooled survival models were used to estimate cumulative incidence of progression to arthritis.Results 293 full-text articles fulfilled screening criteria and 26 were eligible for meta-analysis. The presence of serum autoantibodies confers between a 3.1--19.3-fold increase risk of developing RA. Prospective studies of anticyclic citrullinated peptide 2 (CCP2) or CCP3 positive individuals were grouped according to additional criteria; presence of arthralgia, presence/absence of immunoglobulin M rheumatoid factor (IgM-RF) and first-degree or second-degree relatives with RA. The estimated cumulative incidence of RA at 12 months was highest for CCP2 positive individuals with arthralgia and IgM-RF, at 35.2% (95% CI 29.3% to 41.2%).Conclusion A considerable number of autoantibodies have been examined as predictors for RA; however, the fastest rate of progression to RA in this study occurred in those with CCP2 and IgM-RF in combination with arthralgia. Importantly, the risk of developing RA changes over time for individuals with arthralgia, and they are at the highest risk of progression within the first 24 months of follow-up.PROSPERO registration number CRD42021231245.",
  "authors": [
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Sumera Qureshi"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Maryam Adas"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Phoebe J Cope"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "Hassan Mahfouz"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Katie Bechman"
    },
    {
      "affiliations": [
        "Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "Kevin D Deane"
    },
    {
      "affiliations": [
        "Arthritis Centre, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Hani El-Gabalawy"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK"
      ],
      "name": "Paul Emery"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Axel Finckh"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland"
      ],
      "name": "Benoît Thomas P Gilbert"
    },
    {
      "affiliations": [
        "Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "V Michael Holers"
    },
    {
      "affiliations": [
        "NIHR Newcastle Biomedical Research Centre at Newcastle-upon-Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle-upon-Tyne, UK"
      ],
      "name": "John D Isaacs"
    },
    {
      "affiliations": [
        "Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Alf Kastbom"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK"
      ],
      "name": "Kulveer Mankia"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Division of Rheumatology, College of Medicine, University of Nebraska Medical Center",
        "Medicine, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA"
      ],
      "name": "Ted R Mikuls"
    },
    {
      "affiliations": [
        "Newcastle Biomedical Research Centre at Newcastle-upon-Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle-upon-Tyne, UK"
      ],
      "name": "Arthur G Pratt"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany",
        "Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany"
      ],
      "name": "Juergen Rech"
    },
    {
      "affiliations": [
        "NIHR Advanced Fellow, Centre for Rheumatic Diseases, King’s College, London, UK"
      ],
      "name": "Mark D Russell"
    },
    {
      "affiliations": [
        "Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany",
        "Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany"
      ],
      "name": "Georg Schett"
    },
    {
      "affiliations": [
        "Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Leendert A Trouw"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Lund University, Malmö, Sweden"
      ],
      "name": "Carl Turesson"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands"
      ],
      "name": "Marian H van Beers-Tas"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Annette H M van der Helm-van Mil"
    },
    {
      "affiliations": [
        "Reade Center for Rheumatology and Rehabilitation, Department of Clinical Immunology and Rheumatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands"
      ],
      "name": "Dirkjan van Schaardenburg"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Hanna W van Steenbergen"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "René E M Toes"
    },
    {
      "affiliations": [
        "Versus Arthritis Professor of Rheumatology, Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Andrew P Cope"
    },
    {
      "affiliations": [
        "Professor of Rheumatology, Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "James Galloway"
    },
    {
      "affiliations": [
        "Professor of Medical Statistics & Applied Health Research, Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Sam Norton"
    }
  ],
  "title": "Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis",
  "uid": "99b84913-ded4-5783-ac55-3607a5eca2ec"
}