title: Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor.
abstract: BACKGROUND
  The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).
  
  
  METHODS
  We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.
  
  
  RESULTS
  We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.
  
  
  CONCLUSIONS
  HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.
authors.affiliation: Servicio de Reumatología, Hospital Universitario La Paz, Paseo de la Castellana, 261, Madrid, 28046, Spain. abalsa.hulp@salud.madrid.org
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Arancha
authors.initials: A
authors.lastname: Cabezón
authors.forename: Gisela
authors.initials: G
authors.lastname: Orozco
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cobo
authors.forename: Eugenia
authors.initials: E
authors.lastname: Miranda-Carus
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vicario
authors.forename: Emilio
authors.initials: E
authors.lastname: Martín-Mola
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
mesh_terms: D020816:Amino Acid Motifs; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011487:Protein Conformation; D012217:Rheumatoid Factor / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor