HLA-DPB POLYMORPHISMS - GLU-69 ASSOCIATION WITH SARCOIDOSIS

Sarcoidosis is a chronic granulomatous disorder, which is characterize d by the accumulation of activated CD4(+) T lymphocytes (T cells) at d isease sites. There is up-regulation of cell surface expression of MHC molecules in sarcoidosis, and it has been suggested that specific MHC class II alleles are associated with the disease. A study of chronic beryllium disease (CBD), a granulomatous disorder which is pathologica lly similar to sarcoidosis, has identified an association between this disease and the presence of a glutamine residue at position 69 (Glu 6 9+) of the B1 chain of the HLA-DPB molecule. A further study also sugg ested the importance of Glu at position 55 of the same chain. The aims of the present study were to attempt to define MHC class II alleles a ssociated with sarcoidosis by comparison of their frequency in two gro ups of subjects and to compare the frequency of HLA-DPB1 Glu 69+/- and Glu 55+/- alleles in the same subjects. Forty-one subjects with sarco idosis and 76 normal subjects were studied. The polymorphic regions of the class II MHC were identified by PCR in association with sequence- specific oligonucleotide probes. There were no significant differences in the phenotype frequencies of MHC class II or Glu 55+ alleles betwe en the two groups of subjects. However, there was a significant increa se (P=0.02) in the frequency of HLA-DPB1 Glu 69+ alleles compared wit h the control population. We therefore suggest that the presence of a Glu residue at position 69 on the DPB1 chain may play an important rol e in antigen presentation and recognition in chronic granulomatous dis eases.