Objetivo
i) To determine the molecular mechanisms of interaction between environment-polluting metals and the cells of the immune system;
ii) To determine the role of the genes (e.g. human leukocyte antigen (HLA) genes) which regulate the response of the cells of the immune system (e.g. T-lymphocytes) to foreign agents;
iii) To assess the predictive value of HLA-associated DNA markers for the prevention of environment-induced lung disorders by the screening of exposed populations for susceptibility to allergy to metals.
Epidemiologic, clinical and immunologic studies have demonstrated that metals are capable of inducing lung allergy, including asthma, pneumonitis and chronic interstitial lung diseases. Allergy to metals such as gold, nickel and beryllium is maintained by specialized immune cells, i.e. the T-lymphocytes, which specifically recognize these foreign agents and drive the lung reaction against them.
The molecular basis of allergy to metals will be investigated as follows:
i) The mechanisms of recognition of metals by T-lymphocytes will be characterized using permanent T-lymphocyte lines derived from individuals with allergy to metals.
ii) The molecular mechanisms by which HLA-genes dictate the recognition of metals by T-lymphocytes, will be determined using purified HLA molecules and genetically engineered HLA molecule-expressing cells, to identify genetic markers useful in predicting and preventing metal allergy in susceptible individuals.
iii) HLA gene association with the allergy to metals will be determined by analysis of gene frequencies in populations of individuals affected by allergy to metals.
iv) Based upon data obtained from population studies and in vitro experiments, the ability of the HLA-related DNA markers to predict the risk of susceptibility to metal-induced allergy will be evaluated in a pilot study on metal-exposed individuals.
The study is expected to identify the mechanisms of interaction between environmental factors and genetic factors involved in susceptibility to metal-induced allergy. Consequently, it will permit to design new genetic testing protocols for:
i) The identification of risk factors involved in environment-related lung disorders;
ii) The screening of exposed populations to identify susceptible individuals.
Ámbito científico
Convocatoria de propuestas
Data not availableRégimen de financiación
CSC - Cost-sharing contractsCoordinador
41100 Modena
Italia