Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels

Ann Rheum Dis. 2013 Jun;72(6):1032-6. doi: 10.1136/annrheumdis-2012-202377. Epub 2012 Oct 19.

Abstract

Objective: Early diagnosis of rheumatoid arthritis (RA) remains a challenge. Interleukin (IL)-7 is a pleiotropic cytokine that plays a central role in the development and maintenance of T-cells and has been associated with T-cell dysfunction in RA. Serum levels of IL-7 are reduced in both early and established disease. The aim of this study was to determine whether serum IL-7 can identify patients with very early inflammatory joint symptoms who will progress to RA, and to examine whether IL-7 levels predict disease persistence and radiographic progression.

Methods: Patients with inflammatory joint symptoms<6 months followed over 5 years for progression to RA and 80 healthy controls were studied. Baseline IL-7 levels were measured by ELISA.

Results: Of 250 patients, 108 developed RA (ACR 1987- criteria). IL-7 at inclusion was reduced significantly in RA compared with non-RA patients (p=0.009). IL-7 was categorised using the lower limit of the healthy control distribution (10 pg/ml). In multivariate analysis, independent predictors of RA development were: antibodies against citrullinated peptides (ACPA) positivity (p=0.001), IL-7<10 pg/ml (p=0.003) and swollen joint count (p=0.050). In the ACPA-negative subgroup (n=199), the only predictors were: DAS-44 (p=0.001), IL-7<10 pg/ml (p=0.010) and radiographic erosions (p=0.050). At 1-year follow-up, remission (DAS<1.6) was only predicted by ACPA negativity (p=0.019) and IL-7>17 pg/ml at recruitment (p=0.013).

Conclusion: These data demonstrate that low IL-7 levels in patients with recent onset of symptoms may have value as a diagnostic biomarker predicting the progression to RA, particularly in ACPA-negative disease, as well as being related to RA progression.

Keywords: Cytokines; Early Rheumatoid Arthritis; Qualitative research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis / diagnosis
  • Arthritis / immunology
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers
  • Case-Control Studies
  • Cohort Studies
  • Disease Progression
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-7 / immunology*
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • IL7 protein, human
  • Interleukin-7