GST content and activity are usually investigated through affinity chromatography and using 1-chloro-2,4-dinitrobenzene (CDNB) substrate, since most of these enzymes may catalyze reactions. In helminths, the main detoxifying system is mediated by GSTs CYP450, another important system found in animals, is not present in most parasites ( 13). To date, GST activity has been associated with resistance to all main classes of insecticides ( 12). Arthropod GSTs may confer resistance via direct metabolism, sequestration of chemicals, or metabolizing secondary products. Some GSTs also catalyze the selenium-independent reduction of peroxide-containing compounds ( 11). Two kappa-GSTs from Caenorhabditis elegans, were located in peroxisomes and mitochondria, and, by RNA interference experiments, were found to be involved in oxygen consumption and lipid metabolism ( 10). purified a sigma-GST from the helminth Ascaridia galli with homology to a GSH-dependent prostaglandin-H D-isomerase and high activity and specificity in the GSH-dependent isomerization of prostaglandin H to prostaglandin E, a lipid mediator associated with suppression of host immunity ( 9). Other less common functions of GST have been described in invertebrates. The resulting conjugates are less reactive or more water-soluble, facilitating its excretion ( 6– 8). The main enzymatic reaction of GST consists of the conjugation of the thiol group of GSH to chemical electrophilic centers. In this review, we describe some aspects of the biology of GST, analyze their allergenic activity, and explore the structural reasons and clinical impact of their cross-reactivity. Although it is still an unexplored field, immunomodulatory properties have been detected in certain parasite GSTs, of which some of them interfere with type 2 responses or strengthen immunosuppression ( 3– 5). Altogether, it means that it is necessary to determine the allergenic activity of these IgE-binding molecules and the clinical impact of their cross-reactivity, including potential allergic reactions after anti-helminth vaccination. Also, probably because of their abundance and immunogenicity, some helminth GSTs have been evaluated in pre-clinical studies and clinical trials as vaccines to prevent helminthiasis ( 1, 2). They have allergological importance for multiple reasons: several of them are epidemiologically relevant as environmental sensitizers and due to their sequence and structural conservation even among phylogenetically distant species, they may mediate cross-reactivity among invertebrate allergen sources, such as cockroach, house dust mites (HDM), and helminths. Most of these isoenzymes participate in detoxification reactions, coupling reduced glutathione (GSH) to xenobiotics and/or endogenous substances, such as bilirubin and steroids. The IgE cross-reactivity between mite and cockroach GST suggests that GST is a panallergen.Glutathione-S transferases (GSTs) are a part of a ubiquitous family of dimeric proteins that have triggered the interest of different biology-related disciplines due to their involvement in drug resistance, carcinogenesis, and allergy. Native Der p 8 showed 75% and 65% IgE reactivity with sera from Malaysia and Singapore, respectively.Ī high frequency of sensitization to mite GST among allergic subjects was observed but the titres of IgE reactivity were low. Sera from Taiwanese asthmatics showed 96% and 84% IgE reactivity to native Der p 8 and recombinant Der p 8, respectively. At least 8 isoforms of native Der p 8 were detected by two-dimensionalgel and immunoblot analyses. Our Der p 8 cDNA encoded a basic isoform (pI=8.5) containing six polymorphic residues located at positions 46, 106, 149, 160, 167 and 184. IgE cross-reactivity between Der p 8 and cockroach GST was examined by IgE inhibition assays. IgE reactivity to native and recombinant Der p 8 was assessed by ELISA using sera from allergic subjects from Taiwan, Singapore and Malaysia. Native Der p 8 was affinity purified from mite extract. To assess the allergenicity of native and recombinant mite glutathione S-transferase (GST) (Der p 8) and study the IgE cross-reactivity between Der p 8 and cockroach GST.ĭer p 8 cDNA encoding a new isoform was isolated and expressed in yeast. Purified recombinant and native allergens are useful for studies to resolve such problems. Sensitization to mite and cockroach allergens is common, and diagnosis and therapy of allergy can be further complicated by the presence of allergen isoforms and panallergens.
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