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Reduced IL-7 serum titres are associated with progression towards rheumatoid arthritis in less than 6 months inflammatory arthritis
  1. Vincent Goëb1,2,
  2. Philippe Aegerter3,
  3. Edith Villeneuve1,
  4. Jackie Nam1,
  5. Philip G Conaghan1,
  6. Patrice Fardellone4,
  7. Xavier Le Loët2,
  8. Paul Emery1,
  9. Oliver Vittecoq2,
  10. Frédérique Ponchel1
  1. 1Leeds Institute of Molecular Medicine, The University of Leeds, Leeds, UK
  2. 2Rheumatology, Rouen University Hospital, Rouen, France
  3. 3Public health department, Hôpital Ambroise Paré, Boulogne, France
  4. 4Rheumatology, Amiens University Hospital, Amiens, France

Abstract

Background 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 rheumatoid arthritis (RA). Although IL-7 is highly expressed in the joint, we showed that in the serum, levels of IL-7 are reduced in early and established RA patients. We hypothesised that this reduction may have predictive diagnostic value.

Objectives To determine whether IL-7 titres in serum will identify patients that will evolve towards RA from onset of <6 months.

Methods 250 patients with inflammatory joint symptoms of <6 months were recruited. Evolution towards RA was monitored over 5 years. 80 healthy controls. IL-7 levels were measured by ELISA.

Results Expert rheumatologist diagnostic was established over 5 years follow-up: 108 patients developed RA, 20 undifferentiated arthritis (UA), 20 Spondyloarthropathies, 76 other form of rheumatism (including osteoarthritis, CTD, reactive arthritis, gout) and 26 showed no persistence of inflammation. IL-7 at recruitment was reduced significantly only in RA (p<0.009). There was no correlation with any demographic or clinical parameters (age, sex, DAS, CRP, HAQ RF, ACPA, erosion, SE). IL-7 was categorised using the lower limit of the healthy control distribution (10 pg/ml). Using univariate analysis, predictors of RA diagnostic were: ACPA+ (p=0.003), IL-7 <10 pg/ml (p=0.012), CRP (p=0.029), HAQ (0.012), SJC (p=0.021), SE (p=0.031), RF+ (p=0.068). IL-7 levels were however inversely correlated with symptom duration in RA (R= -0.513, p<0.001) but with no other parameter. In multivariate analysis, predictors of RA were: ACPA+ (p=0.001), IL-7<10 pg/ml (p=0.003), SJC (p=0.050). The latest analysis was repeated in the ACPA- only patient (n=193). Predictors were: IL-7<10 pg/ml (p=0.010), DAS (p=0.001), erosion (p=0.050). Remission (DAS<1.6) at 1 year following treatment (HCQ, followed by MTX if required) was only predicted by IL-7>17 pg/ml (upper quartile of IL-7 distribution) at recruitment (p=0.001). A validation cohort is currently being recruited and pilot analysis (n=51) with 12 months follow-up only. Using the American College of Rheumatology-1987 RA criteria, IL-7<10 pg/ml was associated with RA diagnostic (p=0.048, UA=37 and RA=14). Using 2010 EULAR RA criteria, higher IL-7>10 pg/ml was associated with persisting UA (p=0.055, UA_, RA6).

Conclusion These data demonstrate that a reduction of IL-7 in patient with very recent onset of symptoms has potential as diagnostic biomarkers for evolution towards RA, particularly in ACPA- disease

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