Transcriptional frameshifts contribute to protein allergenicity

This breakthrough research conducted by the Genomic Clinical Synergy Group (Genclis) published in the Journal of Clinical Investigation, (Clin Invest. 2020;130(10):5477-5492. https://doi.org/10.1172/JCI126275) reveals the patented mechanism of the Infidelity transcription, a process by which differences in RNA and DNA sequences are analysed to identify translated proteins capable of causing the production of either immunoglobin E, the antibody responsible for most forms of allergies or Immunoglobin G. This process helps the identification of errors in the copy of DNA and RNA allowing the induction of the allergic antibody lgE.

The discovery of a common cause for allergens paves the way for the prevention and treatment of allergies.

Research Abstract:

Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions

Publication

* This publication is produced by a research group that includes the biotechnology company Genclis (Genomic Clinical Synergy).

*H&H group is collaborating with Genclis in other innovation projects.