Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 1; pp. 248 - 256.e9
• Main Authors: Santiago, Helton C., LeeVan, Elyse, Bennuru, Sasisekhar, Ribeiro-Gomes, Flavia, Mueller, Ellen, Wilson, Mark, Wynn, Thomas, Garboczi, David, Urban, Joseph, Mitre, Edward, Nutman, Thomas B.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2012; Elsevier; Elsevier Limited
• Subjects: allergens; Allergies; allergy; Allergy and Immunology; Amino Acid Sequence; amino acids; Animals; antibodies; Antibodies - blood; antibody formation; Biological and medical sciences; Blattodea; cockroach; Cockroaches - enzymology; Cockroaches - genetics; Cockroaches - immunology; cross reaction; Cross Reactions; cross-reactivity; Elephantiasis, Filarial - immunology; Epidemiology. Vaccinations; Epitope Mapping; epitopes; Female; filariasis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; glutathione; Glutathione Transferase - chemistry; Glutathione Transferase - genetics; Glutathione Transferase - immunology; GST; Heligmosomoides; helminth proteins; Helminth Proteins - chemistry; Helminth Proteins - genetics; Helminth Proteins - immunology; helminths; Helminths - enzymology; Helminths - immunology; Humans; hygiene hypothesis; immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin E - immunology; immunoglobulin G; Immunopathology; Infections; Infectious diseases; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Models, Molecular; molecular mimicry; Molecular Mimicry - immunology; Molecular Sequence Data; Parasites; Parasitic diseases; pathogens; patients; Peptides; Phylogeny; Review boards; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sequence Analysis, DNA; Trichostrongyloidea - immunology; Trichostrongyloidiasis - immunology; Wuchereria bancrofti; Wuchereria bancrofti - enzymology; Wuchereria bancrofti - genetics; Wuchereria bancrofti - immunology; aa; OR; hygiene hypothesis; DMSO; cockroach; filariasis; Fil; GST; allergy; cross-reactivity; 3-D; HbGST; Ni-A; WbGST; HDM; Fil-A; Bla g 5; 3-Dimensional; Filaria-uninfected; Heligmosomoides bakeri GST-2; Fil − and atopic; Amino acid; Fil + and atopic; Filaria-infected; Glutathione-S transferase; House dust mite; GST of Wuchereria bancrofti; GST of the cockroach Blattella germanica; Dimethyl sulfoxide; Odds ratio; Allergy; Immunopathology; Enzyme; Transferases; Parasitosis; Helminthiasis; Hypothesis; Infection; Cockroach; Immunology; Glutathione transferase; Nematode disease; Cross reaction; Helmintha; Molecular mimicry; Sensitization; Filariosis; Invertebrata; Hygiene
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.02.045

The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization. The objective of this study was to investigate the cross-reactivity between a major glutathione-S transferase allergen of cockroach (Bla g 5) and the glutathione-S transferase of Wuchereria bancrofti (WbGST), a major lymphatic filarial pathogen of humans. We compared the molecular and structural similarities between Bla g 5 and WbGST by in silico analysis and by linear epitope mapping. The levels of IgE, IgG, and IgG4 antibodies were measured in filarial-infected and filarial-uninfected patients. Mice were infected with Heligmosomoides bakeri, and their skin was tested for cross-reactive allergic responses. These 2 proteins are 30% identical at the amino acid level with remarkable similarity in the N-terminal region and overall structural conservation based on predicted 3-dimensional models. Filarial infection was associated with IgE, IgG, and IgG4 anti–Bla g 5 antibody production, with a significant correlation between antibodies (irrespective of isotype) to Bla g 5 and WbGST (P < .0003). Preincubation of sera from cockroach-allergic subjects with WbGST partially depleted (by 50%-70%) anti–Bla g 5 IgE, IgG, and IgG4 antibodies. IgE epitope mapping of Bla g 5 revealed that 2 linear N-terminal epitopes are highly conserved in WbGST corresponding to Bla g 5 peptides partially involved in the inhibition of WbGST binding. Finally, mice infected with H bakeri developed anti-HbGST IgE and showed immediate-type skin test reactivity to Bla g 5. These data demonstrate that helminth glutathione-S transferase and the aeroallergen Bla g 5 share epitopes that can induce allergic cross-sensitization.