The influence of HLA-DRB1 alleles encoding the DERAA amino acid motif on radiological outcome in rheumatoid arthritis

Objectives. To investigate the influence of HLA-DRB1 alleles encoding the Q K/RRAA shared epitope (SE) on radiological outcome in rheumatoid arthritis (RA), and to determine whether it is modulated by alleles carrying the puta tive rheumatoid arthritis-protective (RAP) sequence DERAA. Patients and methods. The association between erosive damage and HLA-DRB1 s tatus was examined in 315 RA patients with a disease duration of 5-30 yr. R adiological outcome was measured by scoring X-rays of the hands and feet us ing the standard radiographs of Larsen (Larsen score). HLA-DRB1 typing was carried out using polymerase chain reaction methodology. Results. Patients with two alleles encoding the QK/RRAA SE had significantl y higher Larsen scores than SE-negative patients (96.4 vs 83.3; P = 0.04, a fter correction for multiple testing), with DRB1*0401/*0401 homozygotes dem onstrating the greatest radiological damage (99.9). The lowest Larsen score (65.6) was observed in patients carrying the DERAA motif without an accomp anying SE allele (RAP+/SE-). This was significantly lower than in patients with RAP+/SE+ (105.6, P = 0.04), RAP - /SE - (88.2; P = 0.05) and RAP -/SE (95.8; P = 0.009), after correction for multiple testing. There was no evi dence that the RAP sequence was modulating the effect of the SE since radio logical outcome in RAP+/SE+ patients was not significantly different to tha t in RAP -/SE+ individuals. Conclusions. Our data support a possible role for DRB1 alleles encoding the DERAA motif in protection against severe erosive damage in patients lackin g the QK/RRAA SE, but not in patients heterozygous for the SE. This suggest s that DRB1 alleles encoding the SE have a dominant influence over 'protect ive alleles' and are not merely 'non-protective'.