Role of the Hla-Dp Glu 69 and the Tnf-α Tnfa-α2 Gene Markers in Susceptibility to Beryllium Hypersensitivity

Abstract

Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts, characterized by the accumulation of CD4+ T cells and macrophages in the lower respiratory tract. Beryllium presentation to CD4(+) T cells from patients with berylliosis results in T cell activation, and these Be-specific CD4(+) T cells undergo clonal proliferation and Th1-type cytokine production such as interleukin-2, interferon-gamma and tumor necrosis factor-alpha. In exposed workers, genetic susceptibility to this granulomatous disorder is associated with major histocompatibility gene and the TNF-α gene. The HLA-DP glutamic 69 residue was shown to be the MHC genetic marker associated with disease susceptibility; furthermore the TNF-α TNFA-308*2 allele was found to be independently associated with HLA-DP GIu69 in the determination of berylliosis risk.