A number of studies have indicated that rheumatoid arthritis (RA) is a less severe disease in Mediterranean countries than in Northern Europe. We investigated whether differences in the frequency of class II MHC antigens might contribute to this variation in disease severity.
Typing at HLA-DR and -DQ loci was carried out at low and high resolutions by polymerase chain reaction amplification in patients with early RA of less than 6 months' duration (68 patients in Madrid and 68 in Bath) and in control subjects (929 in Madrid and 226 in Bath). Only ethnic Spanish and British individuals were included as patients and controls.
Shared epitope (SE) alleles represented 19.8 and 28.9% of the total number of class II MHC alleles in controls from Madrid and Bath respectively (P: = 0.00001), this difference being largely due to increased numbers of DRB1*0401 individuals in the British subjects (P: = 0.0000001). Analysis of the patients showed the expected increase in SE alleles when compared with their respective control groups (Madrid, 31.6 vs 19.8%; Bath, 42.6 vs 28. 9%). In Bath the SE was mainly encoded by HLA-DR4 alleles (74.1%), while in Madrid it was encoded almost equally by DR4 (51.1%) and DR1 (44.7%) alleles. The risk of developing RA in carriers of SE alleles was similar in the two cities (Bath, odds ratio 1.83, 95% confidence interval 1.23-2.78; Madrid, odds ratio 1.87, 95% confidence interval 1.25-2.77), and was largely accounted for by HLA-DRB1*0401 alleles.
We conclude that rheumatoid patients in Bath differ from their Spanish counterparts in class II antigen expression and allele frequency. This may be explained partly by genetic differences between the control populations in the two centres, and may help to explain the greater incidence of more severe rheumatoid disease expression seen in RA patients in the UK.