Immunogenetic basis of environmental lung disease: lessons from the berylliosis model.
The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.
Saltini
C
C
Dept di Scienze Mediche, Università di Modena, Italy.
Amicosante
M
M
Franchi
A
A
Lombardi
G
G
Richeldi
L
L
D000818:Animals; D001607:Berylliosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002908:Chronic Disease; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006801:Humans; D007249:Inflammation; D008171:Lung Diseases / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D009784:Occupational Diseases / Q000235:genetics / Q000276:immunology
D006680:HLA Antigens; D006682:HLA-DP Antigens