Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions, Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in similar to3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DP beta -chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DP beta 69, Furthermore, the proliferative responses of the clones were absolutely dependent upon DP beta Glu(69) in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-gamma (Th1) and little or no IL-4 (Th2) cytokines, This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.

Lombardi, G., Germain, C., Uren, J., Fiorillo, M., du Bois, R., Jones Williams, W., et al. (2001). HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease. JOURNAL OF IMMUNOLOGY, 166(5), 3549-3555.

HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease

SALTINI, CESARE;
2001-01-01

Abstract

Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions, Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in similar to3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DP beta -chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DP beta 69, Furthermore, the proliferative responses of the clones were absolutely dependent upon DP beta Glu(69) in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-gamma (Th1) and little or no IL-4 (Th2) cytokines, This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.
2001
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO
English
Con Impact Factor ISI
DEPENDENT DIABETES-MELLITUS; JUVENILE RHEUMATOID-ARTHRITIS; MHC CLASS-II; CELIAC-DISEASE; LUNG-DISEASE; BETA ALLELE; ANTIGEN; GENE; HLA-DR1; HLA-DPB1-ASTERISK-0201
7
Lombardi, G., Germain, C., Uren, J., Fiorillo, M., du Bois, R., Jones Williams, W., et al. (2001). HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease. JOURNAL OF IMMUNOLOGY, 166(5), 3549-3555.
Lombardi, G; Germain, C; Uren, J; Fiorillo, M; du Bois, R; Jones Williams, W; Saltini, C; Sorrentino, R; Lechler, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/56957
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