New research is shedding light on the mechanisms behind the existence of peanut allergies, which “currently affects 3 to 6% of the US population and is increasing in prevalence,” according to a new report published in the journal Science Immunology.
With that in mind, the researchers investigated the underlying cause of peanut allergies by sequencing antibody genes from B-lineage (which produce IgE) plasma cells collected from five body locations in people with peanut allergies.
“We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing.”
The team of researchers, from Stanford University, the University of Cincinnati and Cincinnati Children's Hospital Medical Center, reported that B cells in human food allergy have been studied mostly in the blood, but little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens.
Previous research has linked IgE’s origin to bone marrow, but this research suggests the gut is full of IgE antibodies, which cause severe allergies.
Patients with peanut allergies were assessed by a double-blind placebo-controlled food challenge. The researchers collected samples of B-lineage plasma cells from 19 peanut allergy sufferers who were about to take part in a clinical trial set to test the effectiveness of prescribed doses of peanut proteins for allergy treatment. The researchers studied samples of peripheral blood and endoscopic biopsies of five sites in the GI tract, including proximal esophagus, medial esophagus, distal esophagus, stomach, and duodenum.
The participants were divided into three groups: Peanut allergy, non-food allergy and non-drug allergy (NA).
The team also sequenced the DNA of their tissue, finding shared genetic patterns in the participants. These commonalities suggest people with a peanut allergy might have a similar tendency to produce IgE in response to the nut.
The report notes that at the time of sampling, participants were not receiving immunotherapy for allergies and were avoiding peanut-containing foods.
After sequencing the cells, the researchers found that the cells were being made in the stomach and the duodenum of the small intestine, with high levels of immunoglobulin E antibodies in the guts of those with peanut allergies. Control patients without allergies did not harbor plasma cells that expressed IgE.
The team also reported that their research found evidence of the plasma cells that experienced a class switch recombination (CSR), which involves a cell that stops producing one type of antibody and starts producing another. In this study, IgE. It’s not clear why these cells might be more likely to make this switch in the guts of people with peanut allergies.
“IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE–expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy,” the paper noted.
Better diagnosis, treatment and prevention
The findings could lead to life-changing treatment by giving patients with peanut allergies therapies that target the prevention of CSR. The results could also pave the way for similar therapies for other food allergies.
The research team said they don’t know when these allergy-causing antibodies first show up in the gut, or if they would disappear as allergies diminish.
Source: Science Immunology
06 Mar 2020 Vol. 5, Issue 45 DOI: 10.1126/sciimmunol.aay4209
“Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy”
Authors: R. Hoh et al.