Proteomic and Immunochemical Characterization of Glutathione Transferase as a New Allergen of the Nematode Ascaris lumbricoides

Abstract

Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy. Glutathione transferases (GSTs) from cockroach and house dust mites are clinically relevant allergens and comparative studies between them and the GST from A. lumbricoides (GSTA) are necessary to evaluate their allergenicity. We sought to analyze the allergenic potential of GSTA in connection with the IgE response to non-parasitic GSTs. IgE to purified GSTs from Ascaris (nGSTA and rGSTA), house dust mites (rDer p 8, nBlo t 8 and rBlo t 8), and cockroach (rBla g 5) was measured by ELISA in subjects from Cartagena, Colombia. Also, multidimensional proteomic approaches were used to study the extract of A. lumbricoides and investigate the existence of GST isoforms. We found that among asthmatics, the strength of IgE levels to GSTA was significantly higher than to mite and cockroach GSTs, and there was a strong positive correlation between IgE levels to these molecules.Specific IgE to GSTA was found in 13.2% of controls and 19.5% of asthmatics. In addition nGSTA induced wheal and flare in skin of sensitized asthmatics indicating that it might be of clinical relevance for some patients. Frequency and IgE levels to GSTA were higher in childhood and declined with age. At least six GST isoforms in A. lumbricoides bind human IgE. Four isoforms were the most abundant and several amino acid substitutions were found, mainly on the N-terminal domain. In conclusion, a new allergenic component of Ascaris has been discovered; it could have clinical impact in allergic patients and influence the diagnosis of mite and cockroach allergy in tropical environments.

Allergens of <b><i>Blomia tropicalis</i></b>: An Overview of Recombinant Molecules

“…The group 8 allergen (GST) of B. tropicalis was identified in 1996 by screening of a B. tropicalis cDNA library and it was later produced as a recombinant protein [60,61,62]. While Blo t 8 has been shown to be clinically relevant in Colombia [60,62], in the USA and Singapore the IgE reactivity to this allergen has been reported to be very low [11,61].…”

Human Helminths and Allergic Disease: The Hygiene Hypothesis and Beyond

“…123 There was found to be a significant positive correlation of antiallergenic (Bla g 5, Der p 8, and Blo t 8) and antiparasite (Ascaris and filarial) GST-specific IgE levels in humans. 123,138 In addition, experimental models have corroborated these findings. For example, Heligmosomoides polygyrus infection induced IgE anti-cockroach GST, 123 and immunization studies with Ascaris antigens induced IgE and Th2 cells against HDM extract.…”

“…120 GSTs are major allergens of HDM, 119 cockroach, 135 mold, 136,137 and parasites. 138,139 Among the 13 classes of canonical GSTs, there are many that show very little amino acid conservation. 140 Even with the small degree of sequence conservation, crossreactivity among parasite and allergenic GST has been demonstrated formally.…”

Inmunorregulación inducida por helmintos: una actualización

“…La mayoría de las molé-culas que se le han purificado han tenido la finalidad de estudiar sus propiedades alergénicas (56,77). PAS-1 es el componente purificado de este helminto más estudiado como inmunomodulador.…”