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Extended report
Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels
  1. Vincent Goëb1,2,
  2. Philippe Aegerter3,4,
  3. Rekha Parmar1,
  4. Patrice Fardellone2,
  5. Oliver Vittecoq5,6,
  6. Philip G Conaghan1,
  7. Paul Emery1,
  8. Xavier Le Loët5,6,
  9. Frédérique Ponchel1
  1. 1Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
  2. 2Department of Rheumatology, Amiens University Hospital, Amiens, France
  3. 3Département de santé publique, AP-HP, Hôpital Ambroise Paré, Boulogne-Billancourt, France
  4. 4Université Versailles St-Quentin, UPRES EA 2506, Paris, France
  5. 5Department of Rheumatology, Rouen University Hospital, Rouen, France
  6. 6Inserm U905, Rouen University, Rouen, France
  1. Correspondence to Professor Paul Emery, Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds LS7 4SA, UK; p.emery{at}leeds.ac.uk

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.

  • Early Rheumatoid Arthritis
  • Cytokines
  • Qualitative research

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