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 histoc ompatibility 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 immun opathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivit y pneumonitis and fibrotic lung disorders, an understanding of the interact ion between environmental factors is crucial to epidemiology, prevention an d treatment of these disorders, Berylliosis is an environmental chronic inflammatory disorder of the lung c aused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the dis ease, 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 disease s, to identify environmental levels of lung immunotoxicants that would he s afe for the entire population and to prevent disease risk associated with o ccupation, manufactured products and the environment, Studies on the associations between human leukocyte antigens and chronic in flammatory lung disorders are reviewed in the context of the berylliosis mo del.