Immunology of chronic beryllium disease

Abstract

The current diagnostic criteria for sensitization and chronic beryllium disease rely on the beryllium lymphocyte proliferation test. By understanding the novel immunologic mechanisms and genetic factors associated with sensitization and chronic beryllium disease, we may improve our ability to detect beryllium health effects with new diagnostics, and hopefully refine therapies for disease.

Role of Genetic Factors in Pulmonary Disease Susceptibility

“…Importantly, a dose-dependent effect of HLA-DPB1E69 alleles has been demonstrated, suggesting that Glu69 is a potential marker of disease severity in addition to overall disease risk (Maier et al, 2003). Although HLA-DPB169 is more frequent in individuals with BeS and CBD, 30e40% of exposed workers carrying HLA-DPB1E69 do not develop CBD or BeS (McCanlies et al, 2004;Maier et al, 2003;Samuel and Maier, 2008). This suggests that other host and environmental factors likely play key roles in the etiology of CBD.…”

Infliximab therapy modulates an antigen-specific immune response in chronic beryllium disease

“…The study was conducted at National Jewish Health (NJH) and the Hospital of University of Pennsylvania (HUP), based on a sarcoidosis trial. 17 We aimed to enroll 20 CBD subjects 2,8,18 on stable doses of corticosteroids and/or methotrexate, with no evidence of active or chronic infection, malignancy, other chronic disease, or past treatment with another biologic with a 3:1 infliximab:placebo ratio administered at 0, 2, 6, 12, 18 and 24 weeks. Of the 13 enrolled subjects, 8 in the infliximab treatment arm and 3 in the placebo arm completed the study, two withdrew before the first infusion before the sponsor stopped the study due to slow recruitment.…”

The role of lymphocyte proliferation tests in assessing occupational sensitization and disease

“…BeS is the immunological precursor to CBD and is diagnosed by demonstration of a beryllium stimulated immune response via the BeLPT. CBD manifests as a granulomatous lung disease and is generally diagnosed based on the demonstration of sensitization to Be manifest either by lymphocyte proliferation responses of the peripheral blood or bronchoalveolar lavage (BAL) cells in response to Be stimulation, and the presence of non-caseating granulomas on lung biopsy [1]. To determine if an individual has CBD, a bronchoscopy is usually required as the BeLPT does not differentiate between CBD and BeS.…”

“…In vivo this process results in a cascade of immunologic events, cytokine release and disease [1]. Lymphocyte proliferation testing has been used to assess hypersensitivity to various materials, but most prolifically with beryllium.…”

“…Proliferation is assessed by the degree of cellular uptake of radiolabeled thymidine. Results are expressed as a stimulation index (SI), a ratio of radiolabeled thymidine uptake in the stimulated, antigen-exposed cells compared to uptake in the unstimulated cells [1]. A positive test is generally identified by two or more SIs exceeding a specific threshold of abnormal.…”