Chapter 9 : Human Berylliosis

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This chapter focuses on the current understanding of beryllium induced chronic beryllium disease (CBD) based on recent insights provided through the investigation of the immune mechanisms responsible for disease development. CBD is a granulomatous disorder that primarily affects the lungs and lymphatics, although skin, liver, heart, and other organs may also be affected. The presenting symptoms of CBD are nonspecific and usually include the insidious onset of a dry, nonproductive cough, dyspnea on exertion, and fatigue. Other symptoms include chest pain, anorexia, weight loss, fever, night sweats, and arthralgias. It has been suggested that this genetic marker be used to potentially exclude individuals from certain workplaces; however, there remain both ethical concerns and appreciation that beryllium sensitization and CBD can occur in individuals who do not possess this genetic susceptibility marker. Studies of T-cell receptor (TCR) repertoire in CD4 T cells from bronchoalveolar lavage (BAL) of CBD patients confirm that these T cells are accumulating in the lung in response to the presence of conventional antigen. Importantly, the DPB1 alleles that mediate presentation of beryllium in culture closely matched those implicated in disease susceptibility, and these studies confirm that the HLA contribution to disease susceptibility is based on the ability of those molecules to bind and present beryllium to T cells. Corticosteroids are the treatment of choice for CBD, with multiple case series’ showing that these drugs alter the clinical course of CBD.

Citation: Fontenot A, Newman L. 2003. Human Berylliosis, p 245-264. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch9

Key Concept Ranking

MHC Class II
Major Histocompatibility Complex
Tumor Necrosis Factor alpha
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Figure 1

Immunopathogenesis of chronic beryllium disease. Following the inhalation of beryllium, macrophages present beryllium to CD4 T cells, resulting in T-cell activation, proliferation, and cytokine production. The CD4 T cells secrete Th1-type cytokines (IL-2 and IFN-γ), whereas the antigen-presenting cells produce TNF-α and IL-6.

Citation: Fontenot A, Newman L. 2003. Human Berylliosis, p 245-264. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch9
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Image of Figure 2
Figure 2

Modeling of the HLA-DP molecule based on the crystal structure of the DR1 molecule. A top view of the DR1 peptide-binding groove with the α-chain and β-chain is shown. The polymorphicc harged residues at positions 55–56 and 69 are also shown. Despite the appearance from the ribbon structure, minimal portions of these polymorphic residues are exposed on the outside or top of the β-chain.

Citation: Fontenot A, Newman L. 2003. Human Berylliosis, p 245-264. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch9
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Generic image for table
Table 1

Industries that utilize beryllium

Citation: Fontenot A, Newman L. 2003. Human Berylliosis, p 245-264. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch9
Generic image for table
Table 2

DP β-chain amino acid sequences of beryllium-presenting and nonpresenting alleles

Citation: Fontenot A, Newman L. 2003. Human Berylliosis, p 245-264. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch9

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