title: The HLA-DRB1 shared epitope is not associated with antibodies against cyclic citrullinated peptide in Chinese patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a destructive autoimmune polyarthritis that has been associated with a group of human leucocyte antigen (HLA)-DRB1 alleles that share a common amino-acid sequence at residues 70-74 called the shared epitope (SE). Recently, anti-cyclic citrullinated peptide (CCP) antibodies have also been reported to be associated with HLA-DR4 and have gained wide acceptance as early diagnostic markers for RA in Caucasian patients. The current study was performed to investigate whether the association between the SE (HLA-DRB1 0401/04/05/10) and anti-CCP antibodies is also present in Chinese Han patients with RA.
  
  
  METHODS
  One hundred and four RA patients and 122 healthy controls were recruited. HLA-DR4 was detected by the sequence-specific primer polymerase chain reaction (SSP-PCR) phototyping method. Anti-CCP antibodies and immunoglobulin M rheumatoid factor (IgM-RF) were measured by enzyme-linked immunosorbent assay (ELISA) and laser nephelometry, respectively.
  
  
  RESULTS
  Of the Chinese patients with RA, 76.5% exhibited anti-CCP antibodies compared with none of the controls (76.5% vs. 0%, p<0.001). The prevalence of the SE was significantly higher in patients with RA compared with controls [p = 0.010, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.16-5.07]. Among the HLA-DR4 alleles, the presence of HLA-DRB1 0401 was significantly higher in RA patients than in controls (p = 0.0118, OR = 9.68, 95% CI = 1.13-448.8). In our study we found that the SE was not associated with production of anti-CCP antibodies (p = 0.2899, OR = 1.920, 95% CI = 0.52-8.89).
  
  
  CONCLUSIONS
  The prevalence of the SE is significantly lower in Chinese RA patients, as compared with previous reports of a study using a Caucasian cohort, indicating that distinct genetic risk factors might be associated with anti-CCP antibody production. These data emphasized the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype.
authors.affiliation: Institute of Rheumatology, Immunology and Allergy, Fudan University.
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y-M
authors.initials: YM
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Guan
authors.forename: S G
authors.initials: SG
authors.lastname: Zheng
authors.forename: H-J
authors.initials: HJ
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002681:China; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000097:blood*; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor