title: The role of the shared epitope in arthralgia with anti-cyclic citrullinated peptide antibodies (anti-CCP), and its effect on anti-CCP levels.
abstract: OBJECTIVE
  Patients presenting with both arthralgia and antibodies to cyclic citrullinated peptide (anti-CCP) have an increased risk of developing rheumatoid arthritis (RA). To further characterise this patient group and shed more light on its relationship with clinically manifest early arthritis and established RA, an immunogenetic and serological analysis was performed.
  
  
  METHODS
  In a group of 111 patients with anti-CCP-positive arthralgia, anti-CCP levels and shared epitope (SE) status were determined. Data were compared with 125 and 128 patients with anti-CCP-positive early arthritis and established RA respectively.
  
  
  RESULTS
  In patients with anti-CCP-positive arthralgia, the frequency of SE allele positivity is significantly lower when compared with anti-CCP-positive early arthritis and established RA (58% vs 80%, and 58% vs 92%, respectively, both p<0.001). Median anti-CCP levels were higher in the group of patients with SE-positive arthralgia compared with the group of patients with SE-negative arthralgia (p = 0.02). Median anti-CCP levels were similar in the groups of patients with SE-positive arthralgia and arthritis.
  
  
  CONCLUSIONS
  The lower frequency of SE positivity in patients with arthralgia compared with patients with RA indicates that, compared with patients who were SE positive, patients who were SE negative as a group go through a longer arthralgia phase, or alternatively have a lower risk for transition from anti-CCP positive arthralgia to RA. Furthermore, the present results suggest that in this early stage the effect of the SE on disease risk may be mediated through higher anti-CCP levels.
authors.affiliation: Jan van Breemen Institute, Department of Rheumatology, Amsterdam, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Bos
authors.forename: J
authors.initials: J
authors.lastname: Ursum
authors.forename: N
authors.initials: N
authors.lastname: de Vries
authors.forename: G M
authors.initials: GM
authors.lastname: Bartelds
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: M T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: I E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.forename: R J
authors.initials: RJ
authors.lastname: van de Stadt
authors.forename: J B A
authors.initials: JB
authors.lastname: Crusius
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: D
authors.initials: D
authors.lastname: van Schaardenburg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018771:Arthralgia / Q000276:immunology*; D001168:Arthritis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide