title: Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goëb
authors.forename: Philippe
authors.initials: P
authors.lastname: Aegerter
authors.forename: Rekha
authors.initials: R
authors.lastname: Parmar
authors.forename: Patrice
authors.initials: P
authors.lastname: Fardellone
authors.forename: Oliver
authors.initials: O
authors.lastname: Vittecoq
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Loët
authors.forename: Frédérique
authors.initials: F
authors.lastname: Ponchel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000175:diagnosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508605:IL7 protein, human; D015851:Interleukin-7
keywords: Cytokines; Early Rheumatoid Arthritis; Qualitative research