Role of the berylliosis-associated HLA-DPGlu69 supratypic variant in determining the response to beryllium in a blood T-cells beryllium-stimulated proliferation test.

Background and Aim of the Work: Exposure to beryllium (Be) compounds may cause sensitization as revealed by blood T-cell proliferation against Be in a standardized Be-stimulated T-cell proliferation test (BeLPT). Further, susceptibility to Be hypersensitivity has been associated with the expression of HLA-DP allelic variants carrying a glutamate residue at position 69 of the beta-chain (HLA-DPGlu69) in more than 80% of affected subjects and, at lower frequency, with other HLA-DP, -DQ and -DR alleles/polymorphisms. The aim of this study was to assess whether heterozygous or homozygous carriage of the HLA-DPGlu69 marker may dictate the intensity of the T-cell response to Be in vitro.
Methods: The results of the blood Be-LPT, performed in a single laboratory on 165 subjects (86 Be-exposed controls, 38 Be-sensitized without lung granulomas and 41 berylliosis cases) identified at a single large Be production factory, were analyzed for their realtionship with the HLA-DPGlu69 status as determined by high resolution HLA-DP typing.
Results: Be-sensitized subjects carrying HLA-DPGlu69 presented a significantly higher T-cell response to Be (mean SI: 24.6 +/- 38.7) than the HLA-DPGlu69-negative subjects (mean SI: 11.8 +/- 6.6, p = 0.021). Furthermore, HLA-DPGlu69-positive subjects presented a higher frequency of positive Be-LPT tests (mean frequency 0.36 +/- 0.23) compared to the HLA-DPGlu69-negatives (mean frequency: 0.22 +/- 0.15; p = 0.002). HLA-DPGlu69 homozygosity was not associated with an increased response to Be in the BeLPT CONCLUSIONS: These results indicate that the expression of HLA-DPGlu69 determines higher T-cell proliferation rates and more consistent resposes to Be in vitro in the BeLPT test, both in the homozygous and the eterozygous state, possibly leading to an underestimation of the numbers of HLA-DPGlu69-negative sensitized subjects within exposed populations.