Chronic
beryllium disease (CBD), an irreversible, debilitating granulomatous
lung disease is caused by exposure to
beryllium. This occupational hazard occurs in primary production and machining of Be-
metal, BeO,
beryllium - containing
alloys, and other
beryllium products. CBD begins as an MHC Class II-restricted, T(H)1
hypersensitivity, and the
Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of
HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of
HLA-DPB1 that confers a different magnitude of risk for chronic
beryllium disease:
HLA-DPB1*0401 (OR approximately 0.2),
HLA-DPB1*0201 (OR approximately 3), and
HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a
hypersensitivity response to
beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the
HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to
beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the
HLA-DPB1*1701 transgene product is an important risk factor for induction of the
beryllium-sensitive phenotype. This model should be a useful tool for investigating
beryllium sensitization.