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

D. L. Mattey, A. B. Hassell, M. J. Plant, N. T. Cheung, P. T. Dawes, P. W. Jones, W. Thomson, K. V. Poulton, A. H. Hajeer, W. E R Oilier

    Research output: Contribution to journalArticlepeer-review


    Objective. To investigate the influence of HLA-DRB1 alleles encoding the QK/RRAA shared epitope (SE) on radiological outcome in rheumatoid arthritis (RA), and to determine whether it is modulated by alleles carrying the putative rheumatoid arthritis-protective (RAP) sequence DERAA. Patients and methods. The association between erosive damage and HLA-DRB1 status was examined in 315 RA patients with a disease duration of 5-30 yr. Radiological outcome was measured by scoring X-rays of the hands and feet using 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 significantly higher Larsen scores than SE-negative patients (96.9 vs 83.3: P = 0.04, after correction for multiple testing), with DRB1*0401/*0401 homozygotes demonstrating the greatest radiological damage (99.9). The lowest Larsen score (65.6) was observed in patients carrying the DERAA motif without an accompanying 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 evidence that the RAP sequence was modulating the effect of the SE since radiological outcome in RAP+/SE+ patients was not significantly different to that 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 lacking the QK/RRAA SE, but not in patients heterozygous for the SE. This suggests that DRB1 alleles encoding the SE have a dominant influence over 'protective alleles' and are not merely 'non-protective'.
    Original languageEnglish
    Pages (from-to)1221-1227
    Number of pages6
    Issue number12
    Publication statusPublished - Dec 1999


    • HLA-DRB1
    • Protective alleles
    • Radiological outcome
    • Rheumatoid arthritis
    • Shared epitope


    Dive into the research topics of 'The influence of HLA-DRB1 alleles encoding the DERAA amino acid motif on radiological outcome in rheumatoid arthritis'. Together they form a unique fingerprint.

    Cite this