Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting

Elizabeth A. Bemis, M. Kristen Demoruelle, Jennifer A. Seifert, Kristen J. Polinski, Michael H. Weisman, Jane H. Buckner, Peter K. Gregersen, Ted R. Mikuls, James R. Odell, Richard M. Keating, Kevin D. Deane, V. Michael Holers, Jill M. Norris

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objectives Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting. Methods We screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA. Results 304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2-7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01). Conclusions These findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

Original languageEnglish (US)
Pages (from-to)154-161
Number of pages8
JournalAnnals of the rheumatic diseases
Volume80
Issue number2
DOIs
StatePublished - Feb 1 2021

Keywords

  • ant-CCP
  • epidemiology
  • rheumatoid arthritis
  • rheumatoid factor
  • synovitis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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