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Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort
  1. Jacques-Eric Gottenberg1,
  2. Jean-Michel Dayer2,
  3. Cedric Lukas3,
  4. Beatrice Ducot4,
  5. Gilles Chiocchia5,
  6. Alain Cantagrel6,
  7. Alain Saraux7,
  8. Pascale Roux-Lombard8,
  9. Xavier Mariette8,9
  1. 1Department of Rheumatology, EA 4438, Strasbourg University Hospital, Strasbourg, France
  2. 2Faculty of Medicine, University of Geneva, Switzerland
  3. 3Department of Rheumatology, Lapeyronie Hospital, Montpellier, France
  4. 4Institut Pour la Santé et la Recherche Médicale (INSERM) U1018, Service d’Epidémiologie, Université Paris-Sud, Bicetre Hospital, Le Kremlin Bicetre, France
  5. 5Institut Cochin (INSERM U1016, CNRS UMR8104 and Université Paris Descartes, Paris, France
  6. 6Department of Rheumatology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
  7. 7Université de Brest, Faculté de Médecine et des Sciences de la Santé, EA 2216; CHU Brest, Department of rheumatology, Brest, France
  8. 8Division of Immunology and Allergy, Department of Internal Medicine, Geneva University Hospitals, Switzerland
  9. 9Service de Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud, INSERM U 1012, Le Kremlin Bicêtre, France
  1. Correspondence to Jacques-Eric Gottenberg Department of Rheumatology, EA 4438, Strasbourg University Hospital, Hôpital Hautepierre, 1 Avenue Molière, 67000 Strasbourg, France; jacques-eric.gottenberg{at}


Objective To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation.

Methods Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit.

Results Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression.

Conclusion Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

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  • Funding An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the ESPOIR cohort. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Abbott, Amgen and Wyeth have also provided funding for the ESPOIR cohort study. A grant from the French Society of Rheumatology and from Roche allowed us to assay markers of B cell activation.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Montpellier Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.