title: HLA-DRB1*0404 is strongly associated with high titers of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis.
abstract: OBJECTIVE
  To test whether the presence of RA associated HLA-DRB1*0101, HLA-DRB1*0401 and HLA-DRB1*0404 alleles individually influences anti-cyclic citrullinated peptide antibodies (anti-CCP) production.
  
  
  METHODS
  The frequency of anti-CCP antibodies was calculated in the sera of 260 RA patients expressing either two (double dose genotypes SE+/SE+), one (single dose genotypes SE+/SE-) or no RA associated HLA-DR alleles (SE-/SE-). Anti-CCP antibodies titers were also determined.
  
  
  RESULTS
  RA associated HLA-DR alleles are not mandatory for production of anti-CCP. We found that 68% of SE-/SE- patients were anti-CCP positive. There was no significant difference in anti-CCP between SE negative patient (SE-/SE-) and patients expressing at least one SE (SE+/SE+ and SE+/SE-) (p=0.140). We observed no statistical difference in anti-CCP between RA patients expressing one or two SE (82% vs. 77%, p=0.577). Among SE+/SE-patients, HLA-DRB1*0404 was associated with anti-CCP with a statistically significant difference compared with SE negative patients (90% anti-CCP positive, p=0.02). HLA-DRB1*0404 was also associated with high titers of anti CCP with a statistically significant difference compared with HLA-DRB1*0401 and HLA-DRB1*0101 patients (p=0.025).
  
  
  CONCLUSIONS
  The RA-associated HLA-DRB1*0404 allele was the most strongly associated with the presence of anti-CCP in RA sera. Moreover, HLA-DRB1*0404 patients had higher titers of anti CCP than patients with other RA associated HLA-DR alleles.
authors.affiliation: INSERM UMR 639, Université de la Méditerranée and Rheumatology, APHM, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Charpin
authors.forename: N
authors.initials: N
authors.lastname: Balandraud
authors.forename: S
authors.initials: S
authors.lastname: Guis
authors.forename: C
authors.initials: C
authors.lastname: Roudier
authors.forename: E
authors.initials: E
authors.lastname: Toussirot
authors.forename: J
authors.initials: J
authors.lastname: Rak
authors.forename: N
authors.initials: N
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Reviron
authors.forename: J
authors.initials: J
authors.lastname: Roudier
authors.forename: I
authors.initials: I
authors.lastname: Auger
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; C488436:HLA DRB1*04:04 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide