ASSOCIATIONS BETWEEN SERUM ANTI-CCP ANTIBODY, RHEUMATOID FACTOR LEVELS AND HLA-DR4 EXPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: The diagnosis of rheumatoid arthritis (RA) depends on clinical symptoms, laboratory investigations and imaging. Several autoantibodies, including IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) have been associated with disease activity and/or prognosis of RA. While RF has low specificity, the presence of anti-CCP antibodies is highly specific and sensitive for RA. Among MHC class II molecules, various HLA-DR1 and DR4 alleles ("shared epitope", SE) have been associated with susceptibility to RA. There may be an association between HLA-DR4 positivity and the production of anti-CCP antibody. The presence of one or two SE alleles has been associated with anti-CCP antibody positivity. Moreover, unfavourable disease progression has been related to anti-CCP production and SE positivity. However, there is little information available regarding possible associations between serum anti-CCP antibody levels and HLA-DRB1 expression.Objectives: In this study, we investigated associations of SE positivity with anti-CCP positivity and serum levels. In addition, this is the first report on the possible relationship between SE and anti-CCP in Hungarian RA patients.Methods: Serum anti-CCP, RF and CRP levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.Results: Thirty-three out of 53 patients (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF positivity (χ2=6.717; p<0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (χ2=5.828; p<0.01). There was no correlation between RF positivity and serum levels, CRP serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with SE positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (p<0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE negative patients (76.8 ±56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, 6 out of 6 patients (100%) carrying DRB1*15 alleles and 6 out of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (p<0.01).Conclusion: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus patients carrying HLA-DRB1*04 alleles exhibited an overall 10-fold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations and SE positivity have been related to more rapid disease progression and unfavourable outcome.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 299Session: Humoral aspects – autoantibodies