title: Associations between serum anti-CCP antibody, rheumatoid factor levels and HLA-DR4 expression in Hungarian patients with rheumatoid arthritis.
abstract: BACKGROUND
  The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA. In addition, these alleles may also have relevance for disease outcome. Anti-CCP antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information regarding a relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.
  
  
  OBJECTIVE
  To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.
  
  
  METHODS
  Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.
  
  
  RESULTS
  Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 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 shared epitope 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) compared to SE-negative patients (76.8 +/- 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 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).
  
  
  CONCLUSIONS
  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 tenfold 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 were related to more rapid disease progression and unfavorable outcome.
authors.affiliation: Laboratory of Immunology, Third Department of Medicine, University of Debrecen Medical Centre, Debrecen, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Kapitány
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szabó
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lakos
authors.forename: Magdolna
authors.initials: M
authors.lastname: Aleksza
authors.forename: Anikó
authors.initials: A
authors.lastname: Végvári
authors.forename: Lilla
authors.initials: L
authors.lastname: Soós
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Karányi
authors.forename: Sándor
authors.initials: S
authors.lastname: Sipka
authors.forename: Gyula
authors.initials: G
authors.lastname: Szegedi
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szekanecz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005838:Genotype; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood*
chemical_list: D001323:Autoantibodies; D015804:HLA-DR4 Antigen; D010456:Peptides, Cyclic; D002097:C-Reactive Protein; D012217:Rheumatoid Factor