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


OBJECTIVE
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 (∼ 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.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park , NC.
Geoffrey A
GA
Mueller
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park , NC.
Lars C
LC
Pedersen
INDOOR Biotechnologies, Inc. Charlottesville, VA.
Jill
J
Glesner
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park , NC.
Lori L
LL
Edwards
Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.|Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia.
Josefina
J
Zakzuk
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park , NC.
Robert E
RE
London
Ribeirão Preto Medical School, University of São Paulo, Brazil.
Luisa Karla
LK
Arruda
INDOOR Biotechnologies, Inc. Charlottesville, VA.
Martin D
MD
Chapman
Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.|Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia.
Luis
L
Caraballo
INDOOR Biotechnologies, Inc. Charlottesville, VA.
Anna
A
Pomés
D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D060829:Arthropod Proteins / Q000276:immunology*; D003058:Cockroaches; D003429:Cross Reactions; D003460:Crystallization; D005982:Glutathione Transferase / Q000276:immunology*; D006376:Helminths; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D019476:Insect Proteins / Q000276:immunology*; D051379:Mice; D018716:Molecular Mimicry; D009656:North America; D057089:Pathology, Molecular; D044382:Population Groups; D039981:Pyroglyphidae; D014329:Tropical Climate
D000485:Allergens; D039741:Antigens, Dermatophagoides; D000947:Antigens, Helminth; D060829:Arthropod Proteins; C575000:Bla g 5 allergen, Blattella germanica; C477068:Dermatophagoides pteronyssinus antigen p 8; D019476:Insect Proteins; D007073:Immunoglobulin E; D005982:Glutathione Transferase
Cockroach; cross-reactivity; diagnosis; glutathione S-transferases (GST); helminth; house dust mite