A prospective cohort study of 14-3-3η in ACPA and/or RF-positive patients with arthralgia

Arthritis Res Ther. 2016 Apr 1:18:76. doi: 10.1186/s13075-016-0975-4.


Background: 14-3-3η (eta) is a novel serum/plasma protein biomarker involved in the upregulation of inflammatory and joint damage factors. We analysed the association of 14-3-3η with the development of clinically apparent arthritis in a cohort of subjects with arthralgia and positivity for at least one serologic marker: rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA).

Methods: Measurement of 14-3-3η in plasma collected on entry into the cohort. For this study, 144 subjects with a minimum of 2.5 (median and maximum 5) years of follow-up were available. The relationship between presence and levels of 14-3-3η and development of arthritis was investigated.

Results: Arthritis occurred in 43 (30 %) of the 144 subjects after a median of 15 months. 14-3-3η was detectable up to 5 years before onset of clinical arthritis and was present significantly more often (36 % versus 14 %; relative risk 2.5, 95 % confidence interval 1.2-5.6; p = 0.02) and at significantly higher levels (median 0.95 versus 0.28 ng/ml; p = 0.02) in subjects developing arthritis compared with those who did not. 14-3-3η levels/positivity and ACPA, but not RF, were univariately associated with the development of arthritis while generalized linear model analysis with RF and ACPA as obligatory factors could not return an incremental benefit with 14-3-3η.

Conclusions: 14-3-3η was detectable prior to the onset of arthritis and was associated with arthritis development in arthralgia subjects pre-selected for positivity of RF or ACPA. Its power to predict onset of arthritis independent of ACPA and RF requires a new study in which patients are not pre-selected based on ACPA and/or RF seropositivity.

Keywords: 14-3-3ŋ protein; Anti-citrullinated protein antibodies; Arthralgia; Prediction; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / blood*
  • Adult
  • Aged
  • Arthralgia / blood*
  • Arthralgia / immunology
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Autoantigens / immunology
  • Biomarkers / blood*
  • Cohort Studies
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Prospective Studies
  • Rheumatoid Factor / blood


  • 14-3-3 Proteins
  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • Peptides, Cyclic
  • YWHAH protein, human
  • Rheumatoid Factor