Analysis of glutathione S-transferase allergen cross-reactivity in a North American population: Relevance for molecular diagnosis

Abstract

Background It is not clear if cross-reactivity or co-sensitization to glutathione S-transferases (GST) occurs in tropical and subtropical environments. In the United States, Bla g 5 is the most important GST allergen, and lack of co-exposure to GST from certain species allows a better assessment of cross-reactivity. Objectives To examine the molecular structure of GST allergens from cockroach (Bla g 5), dust mites (Der p 8, Blo t 8) and helminth (Asc s 13) for potential cross-reactive sites, and to assess the IgE cross-reactivity of sensitized patients from a temperate climate for these allergens for molecular diagnostic purposes. Methods Four crystal structures were determined. Sera from cockroach and mite allergic patients were tested for IgE reactivity to these GST. A panel of six murine anti-Bla g 5 mAb was assessed for cross-reactivity with the other three GST using antibody binding assays. Results Comparisons of the allergen structures, formed by two-domain monomers that dimerize, revealed few contiguous regions of similar exposed residues, rendering cross-reactivity unlikely. Accordingly, anti-Bla g 5 or anti-Der p 8 IgE from North American patients did not recognize Der p 8 or Bla g 5, respectively, and neither showed binding to Blo t 8 or Asc s 13. A weaker binding of anti-Bla g 5 IgE to Der p 8 versus Bla g 5 (~100-fold) was observed by inhibition assays, similar to a weak recognition of Der p 8 by anti-Bla g 5 mAb. Patients from tropical Colombia had IgE to all four GST. Conclusions The lack of significant IgE cross-reactivity among the four GST is in agreement with the low shared amino acid identity at the molecular surface. Each GST is needed for accurate molecular diagnosis in different geographic areas.

Epitope Mapping of Rhi o 1 and Generation of a Hypoallergenic Variant

“…These two IgE-reactive peptides of Rhi o 1 were not conserved in other allergen sequences (data not shown) and therefore probably non-cross-reactive in nature. Our study sustains the lower clinical relevance of cross-reactivity between moderately conserved allergens (37). Therefore, epitope information generated in this study may be sufficient for the molecular diagnosis of Rhi o 1 allergy and may not be compromised due to its cross-reactivity with Bla g 2.…”

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].…”

“…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]. Structural models of Blo t 8, and of Asc l 13, the GST of A. lumbricoides , revealed several patches of conserved and surface-exposed residues, suggesting the existence of cross-reactive and species-specific epitopes [60].…”

Human Helminths and Allergic Disease: The Hygiene Hypothesis and Beyond

“…[116][117][118][119][120][121][122][123][124][125][126][127][128] We have demonstrated that helminth infection can be associated with increased IgE responses to many different allergens, especially those structurally related to parasite antigens. 116 Individuals infected with filarial parasites were shown to have higher levels of IgE against HDM and cockroach extracts (that have several major allergens with homologues in filarial parasites) but not against timothy grass extract, an allergen extract with just a few minor allergen homologues in helminths.…”