Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients.

BACKGROUND

A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.

SUBJECTS AND METHODS

In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.

RESULTS

There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 x 10(-36)). Most notably, DRB101, DRB103 and DRB114, clearly differed in LS and non-LS patients. In relation to disease course, DRB107, DRB114 and DRB115 generally associated with, while DRB101 and DRB103 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB103 (good prognosis) dominated over that of DRB115 (bad prognosis).

CONCLUSIONS

We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.