Investigation of the relationship between the HLADRB1 genotype and the presence of autoantibody to cyclic-citrullinated peptide in patients with rheumatoid arthritis

Background

The aetiology of rheumatoid arthritis (RA) has been suggested to be an interaction between genetic and environmental factors. Genetic susceptibility to this disease in most of the population is associated with MHC II molecules that contain an amino acid motif known as the shared epitope (SE). These MHC molecules may bind arthritogenic peptides for presentation to autoreactive T cells. The nature of the arthritogenic peptide is not known, but recent studies have identified post-translationally modified proteins containing citrulline as targets of anti-cyclic-citrullinated peptide (anti-CCP) autoantibodies. It has been shown that in HLA-DRB1*0401 transgenic mice the conversion of arginine to citrulline at the peptide side chain position interacting with the SE significantly increases peptide–MHC affinity and leads to the activation of CD4⁺ T cells in the transgene mice.

Objective

The aim of this work was to investigate the relationship between the HLADRB1 genotype and the presence of anti-CCP IgG antibodies in sera of patients with RA.

Methods

HLA-DRB1 genotyping was performed using PCR seqence-specific primers from the DR low resolution kit and DRB1*01, DRB1*04 subtyping kits as well.

IgG anti-CCP antibody levels were measured by the ImmunoscanRA ELISA kit. Rheumatoid factor was determined by the nephelometric method (Behring). Samples of 131 patients with RA were investigated.

Results

SE is present in 75 (57.2%) and absent in 56 (42.7%) patients. The prevalence of anti-CCP autoantibodies is significantly higher in the group of SE-positive patients (n = 44, 76%) than in the group of non-SE carriers (n = 28) (P = 0.03; chi-squared test). The average autoantibody level measured in anti-CCP-positive patients carrying SE is 742.7 U/ml while in the absence of SE alleles it is 437.5 U/ml, which does not differ statistically.

Conclusion

Association of the SE and citrullinated antigens may be one of the triggers initiating the production of anti-CCP antibodies