Scientists Discover a Peanut Allergy ‘Fingerprint’ That May Help Push Emerging Treatment to New Levels

Research By Krishna Roskin, PhD, Scott Boyd, MD, PhD

Post Date: March 9, 2020 | Publish Date: March 5, 2020

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This image shows IgE+ plasma cells, the cells producing allergy-associated IgE antibodies. IgE is shown as green, and a plasma cell marker is shown as red. IgE+ plasma cells have both green and red staining, appearing as yellow/orange in the image. Nuclei of all the cells in the image are stained blue. Image courtesy of Sushama Varma, Department of Pathology, Stanford University.

About 1 million families in the United States live with the fear that their child might break into hives or feel their throats begin to swell shut from severe allergic reactions to peanut exposure.

While the U.S. Food and Drug Administration approved the first therapeutic, an oral immunotherapy, for the treatment of peanut allergy in January, scientists say much more research is needed to eliminate the threat of severe reactions from peanut allergies.

On March 26, 2020, Science will host a Facebook Live event focused on Hoh et al.’s work and on peanut allergy more broadly. Reporters and the public are welcome. Event to be hosted here: https://www.facebook.com/ScienceMagazine

Expanded IgE+ clonal lineages in multiple tissue sites

Expanded IgE+ clonal lineages in multiple tissue sites

(A) IgE+ clone counts in tissue (squares) and overlapping between tissues (circles). (B) Percentage of clones with IgE members in both indicated tissues, with denominator tissue indicated in the panel upper label. Dots represent PA patients. One outlier value was removed for plotting (42.1% overlap of P107 peripheral blood and stomach). (C) Clonal sharing between tissues (arc segments). Red lines denote clones with IgE+ members (top row) or any isotype (bottom row). Four representative PA patients are shown. (D) Isotype composition of multi-isotype IgE+ clones. (E) Representative clonal lineage from P115. Tissue and isotype are indicated for member nodes. Scale bar indicates IGHV SHM frequency.
Source: Science Immunology 06 Mar 2020.

That work took a significant step forward with new findings published online March 5, 2020, in Science Immunology by researchers at Stanford University, Cincinnati Children’s, and Johns Hopkins University School of Medicine.

The research team collected tissue samples from 19 patients with peanut allergies, then conducted a series of advanced laboratory and bioinformatic analyses to determine which tissues house the immune cells producing the hyper-sensitive antibodies that trigger severe allergic reactions.

The team reports that patients with peanut allergies have a distinctly high concentration of immune cells located in stomach and duodenum, the small intestine adjacent to the stomach, which produce immunoglobulin E (IgE), the antibody type known to be responsible for severe allergic reactions.

This “fingerprint” of peanut allergy sensitivity was not seen as clearly in other locations, such as the esophagus or circulating in the blood. Furthermore, highly similar IgE antibody sequences were identified in multiple individuals with peanut allergy.

“Together, these findings indicate that recognizable and common IgE antibody gene rearrangements are a hallmark of peanut allergy,” the co-authors state. “Such sequence patterns, if replicated and extended beyond our relatively small clinical study, could begin to define a diagnostic set of IgE antibody types that may be specific for particular allergies and could be of value in tracking patient responses to treatment.”

The study was led by first author Ramona Hoh, PhD, and senior author Scott Boyd, MD, PhD, at Stanford.

Krishna Roskin, PhD, a faculty member in the Divisions of Biomedical Informatics and Immunobiology at Cincinnati Children’s designed and created the computational analysis platform used to analyze the antibody sequences. This included software to identify and track clonally related B cells across tissues from next-generation sequencing data.

Publication Information

Original Title:Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy
Published in:Science Immunology
Publish date:March 5, 2020

Read the study

Research By

  • Krishna Roskin, PhD

    Krishna Roskin, PhD

    Divisions of Biomedical Informatics and Immunobiology

    The Roskin Lab combines computational, bioinformatic, and molecular biology methods to study the adaptive immune system.

  • Scott Boyd, MD, PhD

    Stanford University