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

作者：Mueller Geoffrey A; Pedersen Lars C; Glesner Jill; Edwards Lori L; Zakzuk Josefina; London Robert E; Arruda L Karla; Chapman Martin D; Caraballo Luis; Pomes Anna^*

来源：Journal of Allergy and Clinical Immunology, 2015, 136(5): 1369-1377.

DOI：10.1016/j.jaci.2015.03.015

• Cockroach
• house dust mite
• helminth
• glutathione S-transferases (GST)
• cross-reactivity
• diagnosis

Background: It is not clear whether cross-reactivity or cosensitization to glutathione S-transferases (GSTs) occurs in tropical and subtropical environments. In the United States, Bla g 5 is the most important GST allergen and lack of coexposure to GSTs 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 and 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 patients allergic to cockroach and mite were tested for IgE reactivity to these GSTs. A panel of 6 murine anti-Bla g 5 mAb was assessed for cross-reactivity with the other 3 GSTs using antibody binding assays.
Results: Comparisons of the allergen structures, formed by 2-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 (similar to 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 4 GSTs.
Conclusions: The lack of significant IgE cross-reactivity among the 4 GSTs 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.

• 出版日期2015-11