ARS | Publication request: Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization

Submitted to: Journal of Allergy Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 15, 2012
Publication Date: April 15, 2012
Citation: Santiago, H.C., Leevan, E., Bennuru, S., Ribeiro-Gomes, F., Mueller, E., Wilson, M., Wynn, T., Garboczi, D., Urban Jr, J.F., Nutman, T.B. 2012. Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization. Journal of Allergy Clinical Immunology. 130:248-256.

Interpretive Summary: Helminth (worm) parasites can modulate host allergic reactions and either enhance or reduce inflammation including hyper secretion of mucus, airway hyper-reactivity, infiltration of inflammatory cells, and re-structuring of tissues during a repair phase. The study determined that common allergens like those released by cockroaches and designated as Bla g5 were structurally similar to allergens that come from the worm parasite Wuchereria bancrofti that infects humans in some tropical regions of the world. An experimental model was developed that used a worm that infects mice called Heligmosomoides bakeri and that also had proteins that cross reacted with the cockroach Bla g5, to show that the infection would stimulate a greater allergic reactivity to Bla g5. This supported the concept that parasites can sometimes stimulate responses to common allergens that share structural identity with worm products. The information is important to researchers that study the control of infectious diseases in humans and livestock, and the relationship between parasitic infection and allergic disease.

Technical Abstract: The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization. We investigated the molecular and structural similarities between Bla g 5, a major glutathione-S transferase (GST) allergen of cockroaches, and the GST of Wuchereria bancrofti (WbGST), a major lymphatic filarial pathogen of humans. These two proteins are 30% identical at the amino acid level with remarkable similarity in the N-terminal region and overall structural conservation based on predicted three-dimensional models. Filarial infection was associated with anti-Bla g 5 IgE, IgG, and IgG4 Ab production, with a significant correlation between IgE, IgG, and IgG4 Abs to Bla g 5 and WbGST (P < 0.0003). Pre-incubation of sera from cockroach allergic subjects with WbGST partially depleted (by 50 to 70%) anti-Bla g 5 IgE, IgG, and IgG4 Abs. IgE epitope mapping of Bla g 5 revealed that two major N terminal epitopes are highly conserved in WbGST corresponding to Bla g 5 peptides inhibiting WbGST binding. Finally, mice infected with Heligmosomoides bakeri (Hb) developed anti-HbGST IgE and became allergic to Bla g 5 based on skin test reactivity. These data demonstrate that helminth GST and the aeroallergen Bla g 5 share epitopes that induce allergic cross-sensitization.