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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 Centro de Histocompatibilidade do Sul, Lisboa, Portugal
² Unidade de Artrite Reumatóide, Instituto de Medicina Molecular, Faculdade de Medicina, Lisboa, Portugal
³ Unidade de Reumatologia do Hospital de Egas Moniz SA, Lisboa, Portugal
⁴ Departamento de Imunologia da Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal

Correspondence to:
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}netcabo.pt

ABSTRACT
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.

Abbreviations: CCP, cyclic citrullinated peptide; HLA, human leucocyte antigen