title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, EA 4438, Strasbourg University Hospital, Hôpital Hautepierre, 1 Avenue Molière, 67000 Strasbourg, France. jacques-eric.gottenberg@chru-strasbourg.fr
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Cedric
authors.initials: C
authors.lastname: Lukas
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ducot
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
authors.forename: Alain
authors.initials: A
authors.lastname: Cantagrel
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood*; D007378:Interleukins / Q000097:blood*; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D007378:Interleukins; D000098546:Interleukin-21