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.