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Influence of human leucocyte antigen-DRB1 on the susceptibility to rheumatoid arthritis and on the production of anti-cyclic citrullinated peptide antibodies in a Portuguese population
  1. D Ligeiro1,
  2. J E Fonseca2,
  3. O Abade1,
  4. I Abreu4,
  5. M Cruz3,
  6. P Nero3,
  7. J Cavaleiro2,
  8. J Teles2,
  9. H Trindade1,
  10. J M Caetano4,
  11. J Branco3
  1. 1Centro de Histocompatibilidade do Sul, Lisboa, Portugal
  2. 2Unidade de Artrite Reumatóide, Instituto de Medicina Molecular, Faculdade de Medicina, Lisboa, Portugal
  3. 3Unidade de Reumatologia do Hospital de Egas Moniz SA, Lisboa, Portugal
  4. 4Departamento de Imunologia da Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal
  1. Correspondence to:
    Professor J E Fonseca
    Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; jefonseca{at}


Objective: To clarify the influence of the HLA-DRB1 locus on the susceptibility to rheumatoid arthritis and the production of anti-cyclic citrullinated peptide antibodies (anti-CCP) in a Portuguese population.

Methods: 141 patients with rheumatoid arthritis fulfilling the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis were compared with 150 healthy controls. Human leucocyte antigen (HLA)-DRB1 locus genotyping was assessed by polymerase chain reaction reverse probing assays and sequence-specific primers. Anti-CCP antibodies were quantified by ELISA in patients with rheumatoid arthritis. Frequencies between groups were compared by the two-sided Fisher’s exact test and considered significant if p<0.05.

Results: The HLA-DRB1*04 and HLA-DRB1*10 groups were highly associated with rheumatoid arthritis (p<0.001 and p = 0.031, respectively). High titres of anti-CCP antibodies were largely associated with the presence of HLA-DRB1*04/10.

Conclusion: The well-recognised susceptibility alleles to rheumatoid arthritis, HLA-DRB1*04, were associated with rheumatoid arthritis in Portuguese patients. The relatively rare DRB1*10 was also associated with rheumatoid arthritis, as was described previously in other southern European countries. Both groups were associated with high anti-CCP titres, reinforcing its relevance to disease onset.

  • CCP, cyclic citrullinated peptide
  • HLA, human leucocyte antigen

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