Objective. - To investigate the association between the HLA-DRB1 alleles sharing the epitope (Q/R)(K/R)RAA and rheumatoid arthritis (RA) in a large sample of Italian patients (N = 264) recruited from a single centre over the last 5 years.

Methods. - Patients' classification according to the ACR criteria. DNA typing of HLA-DRB1 alleles by conventional polymerase chain reaction sequence specific oligonucleotide probing techniques.

Results. - Low-resolution DRB1 “generic” typing showed a significantly higher frequency of DR4+ RA patients as compared to normal controls. Both DR1 and DR10 specificities were over-represented in our patients, but neither reached the statistically significant P level of 0.05 after Bonferroni's correction. However, direct search of Q(K/R)RAA epitopes, which are present in most DR4+ and DRl+ samples, demonstrated that these motifs were found at increased frequencies in RA patients. Stratification according to gender did not show differences in the proportion of disease-associated HLA alleles.

Conclusions. - Our study confirms the association of HLA-DR4, and -DR1 alleles, and more generally speaking of the shared epitopes Q(K/R)RAA, with disease susceptibility in Italian patients.