HLA-DR alleles associated with disease in Czech and Polish pulmonary sarcoidosis patients

Granuloma formation in sarcoidosis is associated with the accumulation of activated CD4+ T cells at disease sites suggesting the importance of antigen presentation in an MHC class II restricted manner. We have previously demonstrated that the HLA-DR alleles DR14 and DR15 are associated with sarcoidosis in the UK patient population. In this study we examined patients and controls from two further European populations to determine whether shared genetic determinants exist. We examined HLA-DR and -DQ allele frequencies by Polymerase Chain Reaction with Sequence Specific Primers (PCR-SSP). Frequencies for 70 Czech patients, 158 Czech controls and published HLA data for 1867 Czech controls were compared.. Results from 87 Polish patients and 133 Polish controls were also analysed. We found the phenotype frequencies of HLA-DR14 and -DR15 to be raised in the patient groups in both populations. In the Czech groups, 14.3% of patients vs 6.3% of controls (p=0.05) and 5.1% of the published group (p=0.001) were -DR14 positive, while 37.1% of patients vs 29.7% of controls (n.s.) and 24.5% of the published population (p=0.01) were -DR15 positive. In the Polish groups a similar trend was found for -DR14 (5.7% of patients vs 2.3% of controls were -DR14 positive), white 33.3% of patients vs 18.8% of controls were -DR15 positive (p=0.01). Comparison of these results with our UK data also revealed an underrepresentation of the HLA-DR1 allele in all three populations. Patient vs control frequencies were 11.2% vs 19.3% in the UK subjects (p=0.02), 8.5% vs 16.5% (n.s.) and 18.5% (p=0.05) in the Czech patient, control and published control groups respectively, and 10.3% vs 29.3% in the Polish population (p=0.002). These results suggest that similiar genetic associations exist in several European populations, with DR14 and -15 being associated with increased risk, and DR1 associated with protection from sarcoidosis.