The HLA-DRB1 shared epitope is not associated with antibodies against cyclic citrullinated peptide in Chinese patients with rheumatoid arthritis

Scand J Rheumatol. 2008 May-Jun;37(3):183-7. doi: 10.1080/03009740701874444.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Case-Control Studies
  • China
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes* / genetics
  • Epitopes* / immunology
  • Female
  • HLA-DR Antigens / genetics
  • HLA-DR4 Antigen / genetics
  • HLA-DRB1 Chains
  • Humans
  • Immunoglobulin M / blood
  • Male
  • Middle Aged
  • Peptides, Cyclic / blood*
  • Peptides, Cyclic / immunology
  • Polymerase Chain Reaction
  • Rheumatoid Factor / blood*
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • Epitopes
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*04:01 antigen
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor