[Genetic polymorphism of glutathione s-transferase as a factor predisposing to allergic dermatitis].
In the inductive phase of contact allergic dermatitis, simple chemical compounds (haptens) produce together with epidermic proteins adducts presented by Langerhans cells to T lymphocytes. Binding to protein carrier is a necessary condition of transforming a low-molecular allergen into immunogenic one and evoking immunological reaction. The production of allergen adducts with proteins is conditioned by the presence of electrophilic groups in their molecules, or their acquiring during biotransformation phase I. Active allergen metabolites undergo further alterations during biotransformation phase II which leads most frequently to the decline in their chemical activity and more rapid excretion from the body. The number of reactive metabolites (reactive allergens) available for producing adducts with proteins keeps the balance between activation and deactivation reactions. Glutathione S-transferases play a particular role in the allergens (or their metabolites) deactivation process in biotransformation phase II. These enzymes catalyse reactions responsible for the declined electrophilic potential of allergens (or their metabolites), and thus for the decrease in the number of allergen molecules able to produce protein covalent bindings (adducts). Glutathione S-transferases, occurring in the human cellular cytoplasm belong to five classes: alpha(GST A), mu(GST M), theta(GST P), pi(GST T) and Z(GST Z), as well as to one class present in microsomes. The study indicated the presence of isoenzymes GST T1 and GST M1 in the skin. Both isoforms participate in the process of low-molecular allergen biotransformation. Carriers of defective genes GST T1 and/or GST M1 are more vulnerable to allergenic effect of some allergens, e.g. thimerosal, which is associated with the absence of or decrease in the activity of isoenzymes GST T1 and GST M1.
Lutz
W
W
Zakładu Diagnostyki Laboratoryjnej, Instytutu Medycyny Pracy, Łodzi.
Tarkowski
M
M
Nowakowska
E
E
D000485:Allergens / Q000378:metabolism; D001711:Biotransformation; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000201:enzymology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D012307:Risk Factors; D015262:Xenobiotics / Q000378:metabolism
D000485:Allergens; D007527:Isoenzymes; D015262:Xenobiotics; D005982:Glutathione Transferase