Why does the body deem some foods safe and others unsafe?

Amazing stuff!

"Highlights

• Scientists identify three new proteins, one each from soybean, corn, and wheat, that the body uses to determine oral tolerance—the opposite of food allergy
• They found that specialized immune cells called regulatory T cells interact with these proteins in the gut
• By understanding tolerance, researchers can better understand food allergies and begin to imagine future immunotherapies that promote tolerance rather than allergic reactions

...

identifies new bits of food proteins that tell gut immune cells when to tolerate certain foods. They found three of these protein segments, called epitopes—one each from soybean, corn, and wheat. These epitopes interact with specialized immune cells called regulatory T cells to inform that tolerance-or-rejection decision. ..."

"Editor’s summary

Immunological tolerance to dietary antigens is essential for preventing food allergies and digestive disorders such as celiac disease. However, the specific food-derived antigens that contribute to immune tolerance remain poorly described. Blum et al. mapped the dietary epitopes recognized by food-responsive T cell receptors (TCRs) derived from murine intestinal regulatory T (Treg) cells.

Seed storage proteins from corn, wheat, and soy, including the maize protein αZein, were targets of food-responsive Treg cell TCRs. αZein-specific Treg cells suppressed T cell responses to αZein ex vivo and after adoptive transfer into naive mice. These findings provide insight into the dietary components recognized by naturally occurring Treg cells that mediate oral tolerance. ...

Abstract

Food antigens elicit immune tolerance through the action of intestinal regulatory T (Treg) cells. Unlike food allergens, the proteins that mediate tolerance are mostly undescribed.

Here, we found that epitopes derived from seed storage proteins are targets of murine intestinal Treg cells, with the most frequent response targeting the C terminus of the maize protein alpha-zein.

A major histocompatibility complex (MHC) tetramer loaded with this antigen revealed that zein-specific T cells are predominantly intestinal Treg cells, develop concurrently with weaning, and constitute up to 2% of the peripheral Treg cell pool. Zein-responsive Treg cells repressed naïve T cell proliferation ex vivo, and prior dietary exposure resulted in a constrained response upon diverse inflammatory challenges in vivo, supporting a specific role for gut-resident Treg cells in suppressing systemic immune responses.

Our work reveals the development, immune-suppressive characteristics, and function of naturally occurring Treg cells that recognize dietary seed storage proteins, a previously undescribed class of antigens in oral tolerance."

Why does the body deem some foods safe and others unsafe? - Salk Institute for Biological Studies "Study co-led by scientist now at Salk Institute finds three new proteins that the body uses to determine “safe” foods, helping understand food tolerance and allergy"

Identification and characterization of dietary antigens in oral tolerance (no public access)

In developing immunity to allergens, a little ‘dirty’ goes a long way

What has been known for long time gets confirmed again and again! The more and early exposure to potential allergens helps to prevent allergies!

How many more times does this need to be confirmed? This seems to be kind of redundant research!

"... Yale researchers have now found an answer. It turns out that exposure to diverse microbes and proteins early in life creates broad immune memory and a specific antibody that helps block allergic reactions later in life. Rather than overreacting to harmless allergens (ragweed, cats, peanuts, etc.), researchers say, an experienced immune system responds in a balanced way. ...

To find out, researchers compared two groups of mice. One group consisted of mice raised in microbe-rich environments — akin to mice living in a natural habitat. The other group consisted of laboratory mice raised in sterile conditions. Researchers exposed both groups to allergens and then measured allergic reactions, antibody production, and immune cell activity in the animals. ..."

From the abstract:

"Allergic diseases are caused by overexuberant type II immune responses mounted against environmental antigens. The allergic state is typified by the presence of allergen-reactive immunoglobulin E (IgE), which triggers mast cell degranulation upon allergen encounter, manifesting in pruritis, oedema and, in severe cases, anaphylaxis.

Over the past century, the prevalence of allergic diseases has increased markedly, suggesting that environmental rather than genetic factors are mediating this change. Although many hypotheses connecting environment to allergy exist, the biological mechanisms that underpin environmentally mediated protection from allergy are unknown.

Here we show, using a mouse model of allergic disease, that exposure to immunostimulatory environments generated cross-reactive adaptive immune memory, which tracked with obstructed type II immune responses upon allergen exposure. We found that engagement of cross-reactive adaptive immunity protected against future allergic sensitization and suppressed established allergic responses.

Cross-reactivity in a tolerogenic context also prevented allergy, with the effect extending across antigenically complex exposures even at low protein sequence similarity. Our findings demonstrate a mechanistic relationship between environment and allergy, with general implications for adaptive immune function in natural settings."

In developing immunity to allergens, a little ‘dirty’ goes a long way | Yale News "New Yale research finds that microbe-diverse environments build protective immune memory that helps prevent allergies. "

Environmentally driven immune imprinting protects against allergy (open access)

Fig. 2: Pet shop mice have pre-existing immune memory of model antigens.

How to forget allergies

Good news!

"... a new study suggests a possible path towards one: getting the immune cells that produce problematic antibodies to forget what they were doing. ...

Researchers have now discovered that, in mice, if these B cells are exposed to their allergen in the absence of a key molecule called IL-4, they “forget” producing IgEs and make IgGs instead—a phenomenon known as class-switching—and they keep producing IgGs, even when IL-4 returns. ..."

From the Editor’s summary and abstract (a poorly written summary/abstract only for specialists):

"IgE antibodies in allergy are maintained by class switching of IgG1 memory B cells (MBCs) and IgE-fated type 2–polarized MBCs (MBC2s). Whether the type 2 phenotype of MBC2s and the IgE trajectory of allergen-specific MBCs are modifiable is unknown. Bruton et al. determined that IL-4 signaling maintained the MBC2 phenotype and controlled the IgE trajectory of MBCs. IL-4 blockade redirected the recall response to a type 1–like response, producing IgG2c antibodies. Exposure to type 1–polarizing adjuvants during the recall response reprogrammed MBCs generated in a type 2 environment to non-IgE fates, demonstrating the functional plasticity of MBCs. 

Abstract

Long-lived immunoglobulin E (IgE) responses against innocuous environmental and dietary antigens (Ags) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for interleukin-4 (IL-4) responsiveness. The plasticity of the MBC compartment destined for IgE class switch recombination remains poorly understood.

In this work, we report critical IL-4 and IL-13 dependency for the pathogenic IgE fate of type 2–polarized MBCs in allergy. Initiation of a recall response in the absence of IL-4 and IL-13 signaling diminished the type 2 MBC phenotype in mice and humans. This permitted the emergence of long-lived Ag-specific IgG2c+ MBCs in mice. The divergence to a type 1–like response was dependent on interferon-γ signaling and arose from both unswitched and class-switched Ag-specific B cells in vivo. This reprogrammed fate was sustained even beyond therapeutic intervention, revealing fundamental insights into the plasticity of the allergen-specific recall response."

ScienceAdviser

Pathogenic IgE-fated memory B cell responses retain functional plasticity (no public access)

Pathogenic IgE-fated B cell memory retains functional plasticity (preprint, open access, first published November 2023)

Cockroaches release indoor allergens

Cockroaches are more nasty than we have previously known!

"The presence of cockroaches, particularly in lower-income urban households, is a known risk factor associated with the development of allergies or asthma among children. However, a causal relationship between cockroach presence and levels of endotoxins in homes was unclear. Kakumanu et al. addressed this with laboratory assays from apartments in North Carolina. They found that roach feces, especially from females, increased allergen and endotoxin levels in homes. Compared with bedrooms, kitchens had more allergens because they provided the main sources of food for roaches. Importantly, when exterminators eliminated the pests, air quality greatly improved, illustrating the need for effective pest control to protect children’s health."

From the abstract:

"Background

Cockroach allergens are well recognized as important risk factors in the development and prevalence of allergic rhinitis and asthma in children, especially in low-income urban households. The German cockroach gut hosts a diverse community of highly abundant microbes, including gram-negative bacteria that shed large amounts of endotoxins in cockroach feces.

Objective

We sought to delineate the causal relationship between the presence of cockroaches in homes and levels of household endotoxins.

Methods

In laboratory assays, we measured the amount of endotoxin produced by cockroaches.

In-home monitoring estimated the size of the cockroach population in each home and quantified cockroach allergen Bla g 2 and endotoxin levels in household dust and on heating, ventilating, and air-conditioning (HVAC) filters. An environmental intervention was implemented in a subset of the infested homes to eliminate cockroaches. Bla g 2 and endotoxin levels were quantified for 6 months after the intervention.

Results

Large amounts of endotoxin are excreted by female (2900 endotoxin units [EU]/mg feces) and male (1400 EU/mg) cockroaches.

At baseline, household dust and HVAC filters in infested homes had significantly higher levels of allergen (Bla g 2) and endotoxin than uninfested homes. Environmental intervention resulted in significant declines in cockroaches as well as allergen and endotoxin levels. In contrast, cockroach numbers and allergen and endotoxin concentrations remained high in infested-control homes.

Conclusions

Cockroaches are a significant source of both endotoxins and potent allergens, potentially resulting in coexposure of asthmatic children to both."

In Other Journals | Science

Indoor allergens and endotoxins in relation to cockroach infestations in low-income urban homes

Exercise-Induced Urticaria: When People are Allergic to Physical Activity

Amazing stuff! I think I am allergic to allergies! 😊 I guess the good news is that it is very rare. Maybe it is even a medical curiosity.

Could this become a good excuse to avoid physical exercise? 😊

"... First described in the 1970s, exercise-induced urticaria is a relatively rare condition likely due to a sudden increase in the body’s core temperature.

Scientists propose that mast cell degranulation and a rise in plasma histamine levels are involved. In extreme cases, people may experience a systemic reaction where tissues beyond the skin are involved, such as anaphylaxis. The condition can be managed with a regimen of antihistamines and epinephrine administration if required. ...

Another working theory is that an increase in temperature activates the sympathetic nervous system, which is involved in the fight-or-flight response. This stimulates nerve fibers to release the neurotransmitter acetylcholine, leading to mast cell degranulation, and consequently secrete histamine. ..."

Exercise-Induced Urticaria: When People are Allergic to Physical Activity | The Scientist "Some people experience an itchy skin rash or hives after exercising because of immune responses activated by a rise in body temperature."

Figure 2: Urticaria on abdomen within 20 minutes of the onset of the exercise (Source)

Peanut allergies have declined sharply among children. Really!

No kidding! Almost self evident!

"Peanut allergies have declined sharply among children since pediatric guidelines issued in 2017 encouraged parents to introduce infants to peanuts rather than avoid them, per a study published in Pediatrics, which found the rate of peanut allergies among children under 3 plunged from 1.46% in 2012–2015 to 0.93% in 2017–2020."

"In this issue of Pediatrics, Gabryszewski et al provide evidence that efforts to prevent peanut allergy at the population level may be beginning to take hold in the United States. Their analysis, based on electronic health record (EHR) data in the American Academy of Pediatrics (AAP) Collaborative Electronic Reporting database, demonstrates a decline in the incidence of peanut allergy among children born after the publication of the Learning Early About Peanut Allergy (LEAP) trial findings in 2015.2 This is one of the first reports suggesting that clinical research findings and subsequent guidelines on early allergen introduction may be translating into meaningful real-world impact. ..."

Global Health NOW: The Resistance to Ending UNAIDS; Gaza’s Ecological Wounds; and Spreading the Benefits of Child Spacing in Nigeria

Encouraging Trends in Peanut Allergy Prevention: Real-World Impact of Prevention Guidelines (open access)

New, very effective medication for food allergies

Good news!

"... By comparing mice prone to food allergies with ones who never seem to develop them, researchers discovered that molecules in the gut called leukotrienes play a pivotal role in the transport of potential allergens out of the stomach and into the bloodstream, where they can trigger an allergic reaction. ... 

A drug called zileuton, which is already approved for treating asthma, blocks the synthesis of leukotrienes—and sure enough, when her team and another group of researchers gave it to mice, the animals were able to consume foods that they’re allergic to without the life-threatening reaction. ..."

From the editor's summary and abstract:

"Editor’s summary

Cysteinyl leukotrienes (CysLTs) are inflammatory mediators implicated in allergic responses, particularly asthma. Two studies examined the role of CysLTs in the development of anaphylaxis in response to ingested food allergens in mice. Hoyt et al. found that CysLTs promoted the transport of intact food allergens from the gut lumen into the tissue.

Mice that did not experience anaphylaxis had variants of DPEP1, an enzyme that metabolizes CysLTs, linked to augmented enzymatic activity. Batchel et al. found that when cells from the hematopoietic compartment could not synthesize CysLTs, mice had attenuated responses to ingested allergens. Mast cells within the intestinal epithelium could synthesize and respond to CysLTs. In both studies, blocking the synthesis of CysLTs using the drug zileuton before or concurrent with food-allergen exposure prevented the symptoms associated with anaphylaxis in mice ...

Structured Abstract

INTRODUCTION

Allergic reactions to food are mediated by cross-linking of preformed food-specific immunoglobulin E (IgE) antibodies bound to tissue mast cells upon allergen exposure. However, some people who have food-specific IgE do not have any allergic reaction to that food and are considered “sensitized tolerant.” How this population remains unresponsive to allergens is unclear, but understanding the underlying mechanisms could identify approaches for treating food allergy.

RATIONALE

To identify the genetic causes of a sensitized tolerant state, we studied an unexplained aspect of food allergy in mouse models. With rare exceptions, the commonly used C57BL/6 mouse strain demonstrates anaphylaxis to food allergens when challenged systemically, but not orally, despite robust IgE production, thus potentially modeling a sensitized tolerant state.  ...

RESULTS

We found that oral anaphylaxis–resistant C57BL/6 mice have gut barriers that are impermeable to intact food allergens relative to susceptible strains such as C3H/HeJ even before allergic sensitization. ... Using a forward genetic screen of oral anaphylaxis, we identified a ... cysteinyl leukotriene (CysLT) lipid inflammatory molecule. Although CysLTs are important mediators of allergic responses, a mechanistic connection between CysLTs and food allergen transport is unknown. We found that oral anaphylaxis–susceptible mice had elevated CysLTs in the gut, suggesting impaired DPEP1 enzymatic activity. Indeed, blockade of DPEP1 with cilastatin enhanced allergen absorption in anaphylaxis-resistant mice. Conversely, inhibition of leukotriene synthesis with zileuton reduced allergen absorption and prevented anaphylaxis after oral challenge in susceptible mice. ..."

ScienceAdviser

Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice (no public access)

Intestinal mast cell–derived leukotrienes mediate the anaphylactic response to ingested antigens (no public access)

Tuning food allergen transport by gut epithelial cells to trigger anaphylaxis.

Intestinal mast cell differentiation highlights mediator requirements for oral anaphylaxis.

We’re on the verge of a new universal Spring allergy treatment using the monoclonal antibody Omalizumab

Good news! A recommendable survey article!

"... Omalizumab, sold as Xolair, is an asthma medication that was approved more than 20 years ago, but it has proven successful in treating seasonal allergies in recent preliminary trials. So successful, in fact, that now some doctors in the US are prescribing it for certain patients during hay fever season. It is an injection, rather than a pill or a spray, that’s given a couple of weeks before pollen and grass levels start to rise.

One obvious benefit is you get a single shot and enjoy your spring. But even better, omalizumab can forestall allergic reactions at the source. That means an injection could stop all allergic reactions — not only seasonal allergies but food allergies (such as peanuts) and insect allergies for a prolonged period of time. This class of treatment — monoclonal antibodies, special artificial proteins that carry instructions to the body’s immune system — have the potential to be a genuine all-in-one allergy wonder drug. ...

Large clinical trials are underway in China and Japan, which could lead to omalizumab’s approval in those countries for seasonal allergies. The next generation of monoclonal antibody allergy treatments is already in the works. ...

Monoclonal antibodies stop that process before it begins. They deliver artificial proteins that carry instructions to your immune system to block the receptors that create allergic reactions and prevent the overresponse that releases histamine in the first place. ..."

Credits: Global Health NOW: Pandemic Agreement Reached; A Brain Bank Hangs in the Balance; and Spore-Driven Threats

We’re on the verge of a universal allergy cure "The one allergy treatment to rule them all, explained."

Revealed at last: Structure of the antibody-receptor complex common to all IgE-mediated allergic hypersensitivity reactions

Good news!

From the abstract:

"Immunoglobulin E (IgE) binds with high affinity to its receptor, FcεRI, on mast cells and basophils, and cross-linking of allergen-specific IgE by minute amounts of multivalent allergen stimulates a powerful and immediate allergic reaction. In this issue of Science Signaling, Zhang et al. report the three-dimensional structures of the human and murine receptors, with and without bound IgE-Fc, to reveal some intriguing differences between mouse and human in this critical antibody-receptor interaction."

From the editor's summary and abstract:

"Editor’s summary

Binding of immunoglobulin E (IgE) to its high-affinity receptor FcεRI on mast cells and basophils stimulates allergic reactions. The limited number of antibody-based therapies to treat allergies could be expanded by a better understanding of the IgE-bound receptor complex (see the Focus by Sutton). By solving the cryo-EM structures of human and mouse FcεRI bound to IgE-Fc, Zhang et al. found species-specific differences in interactions between IgE and the extracellular domains of the receptors. Unexpectedly, the binding of IgE-Fc to mouse FcεRI caused no conformational changes in the receptor. Together, these findings may inform the development of improved inhibitors of IgE-mediated allergic responses. ...

Abstract

The high-affinity immunoglobulin E (IgE) receptor (FcεRI) drives type I hypersensitivity in response to allergen-specific IgE. FcεRI is a multimeric complex typically composed of one α, one β, and two disulfide-linked γ subunits. The α subunit binds to the fragment crystallizable (Fc) region of IgE (Fcε), whereas the β and γ subunits mediate signaling through their intracellular immunoreceptor tyrosine–based activation motifs (ITAMs). Here, we report cryo–electron microscopy (cryo-EM) structures of the apo state of FcεRI and of FcεRI bound to Fcε. At the transmembrane domain (TMD), the α and γ subunits associate to form a tightly packed, three-helix bundle (αγ2 bundle) with pseudo-threefold symmetry through extensive hydrophobic and polar interactions. The αγ2 bundle further assembles with the β subunit to complete the TMD, from which multiple ITAMs might extend into the cytoplasm for downstream signaling. The apo mouse FcεRI essentially forms an identical structure to that of the Fcε-bound sensitized form, suggesting that the binding of Fcε to FcεRI does not alter the overall conformation of the receptor. Furthermore, the juxtamembrane interaction between the extracellular domains (ECDs) of mouse FcεRIα and FcεRIβ is not observed between their human counterparts, which implies potential species-specific differences in receptor stability and activation. Our findings provide a framework for understanding the general structural principles underlying Fc receptor assembly, the signaling mechanism underlying type I hypersensitivity, and the design of efficient antiallergic therapeutics."

Revealed at last: Structure of the antibody-receptor complex common to all IgE-mediated allergic hypersensitivity reactions | Science Signaling (no public access)

Architecture of the high-affinity immunoglobulin E receptor (no public access)

Mast cells eat other immune cells (neutrophils) during allergic reactions

Amazing stuff! Good news for all suffering from allergies!

"As if immune cells weren’t already weird enough, researchers studying allergic responses in mice have spotted something completely unexpected ... the phenomenon was completely unexpected. ...

“ ... living neutrophils were sitting inside living mast cells,” ...

“This new understanding of how mast cells and neutrophils work together adds a whole new layer to our knowledge of allergic reactions and inflammation. 

“It shows that mast cells can use neutrophils to boost their own capabilities – an aspect that could have implications for chronic allergic conditions where inflammation occurs repeatedly.” ..."

"Known for their role in allergic reactions, mast cells have long been recognised as key players in our immune system. When they encounter allergens, they release chemicals that trigger typical allergy symptoms such as tissue swelling and inflammation. Now, researchers at the Max Planck Institute of Immunobiology and Epigenetics ... have discovered a hidden talent of mast cells: they can capture and use another type of immune cell called neutrophils. This surprising discovery sheds new light on how our immune system works, particularly during allergic reactions."

From the highlights and absract:

"Highlights

• MCs [mast cells] induce neutrophil swarms upon IgE-mediated degranulation in tissues

• Living neutrophils are trapped by MCs and form a cell-in-cell structure

• MITs show increased functional and metabolic fitness

• MITs are more pro-inflammatory and can exocytose active neutrophilic compounds

Summary

Neutrophils are sentinel immune cells with essential roles for antimicrobial defense. Most of our knowledge on neutrophil tissue navigation derived from wounding and infection models, whereas allergic conditions remained largely neglected. Here, we analyzed allergen-challenged mouse tissues and discovered that degranulating mast cells (MCs) trap living neutrophils inside them. MCs release the attractant leukotriene B4 to re-route neutrophils toward them, thus exploiting a chemotactic system that neutrophils normally use for intercellular communication. After MC intracellular trap (MIT) formation, neutrophils die, but their undigested material remains inside MC vacuoles over days. MCs benefit from MIT formation, increasing their functional and metabolic fitness. Additionally, they are more pro-inflammatory and can exocytose active neutrophilic compounds with a time delay (nexocytosis), eliciting a type 1 interferon response in surrounding macrophages. Together, our study highlights neutrophil trapping and nexocytosis as MC-mediated processes, which may relay neutrophilic features over the course of chronic allergic inflammation."

Mast cells eat other immune cells during allergic reactions

Allergy Cells’ Hidden Secret (original press release) "How mast cells trap and use living neutrophils during allergic reactions"

Neutrophil trapping and nexocytosis, mast cell-mediated processes for inflammatory signal relay (open access)

Graphical summary

This scanning electron microscopy image captures the moment where degranulating mast cells (pseudo-coloured in sepia) attract and start to incorporate living neutrophils (pseudo-coloured in cyan), forming cell-in-cell structures where mast cells trap living neutrophils inside them.

A switch to pathogenic IgE production in food allergy found in memory B cells

Good news! Perhaps a breakthrough! Two independent studies come to similar conclusion.

From the editor's summary and abstract:

"Editor’s summary

IgE is the key mediator of allergic responses in the context of both food allergy and allergic rhinitis. However, most IgE-producing cells are short-lived, begging the question: What population replenishes the IgE-producing cell pool? In a pair of papers, Ota et al. and Koenig et al. independently identified a population of type 2–polarized memory B cells expressing IgG1 or IgG4, CD23, and IL-4Rα that also express germline IGHE. Ota et al. found that these cells were enriched in children with peanut allergy as compared with non-allergic pediatric controls, expressed highly mutated B cell receptors specific to peanuts, and had a high ability to switch to IgE in vitro. Koenig et al. identified a comparable cell type in adults with birch allergy, house dust mite allergy, or peanut allergy and found that these memory B cells generated allergen-specific IgE during early sublingual allergen immunotherapy. Together, these studies implicate type 2–polarized memory B cells expressing IgG, CD23, and IL-4Rα as the source of pathogenic, allergen-specific IgE-producing cells. ...

Abstract

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23+IgG1+ memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23+IgG1+ memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of “type 2–marked” IgG1+ memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)– and IL-13–regulated genes, such as FCER2/CD23+, IL4R, and germline IGHE, and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of “type 2–marked” IgG1+ memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+ memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy."

From the abstract:

"Abstract

Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we report a population of type 2–polarized MBCs defined as CD23hi, IL-4Rαhi, and CD32low at both the transcriptional and surface protein levels. These MBC2s are enriched in IgG1- and IgG4-expressing cells while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. Furthermore, MBC2s generated allergen-specific IgE during sublingual immunotherapy, thereby identifying these cells as a major reservoir for IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases but could be beneficial in protection against venoms and helminths."

CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy | Science Translational Medicine (no public access)

Type 2–polarized memory B cells hold allergen-specific IgE memory

Nanoparticle with mRNA appears to prevent, treat peanut allergies in mice

Good news! mRNA keeps on giving!

"Key takeaways

• Peanuts are one of the most common food allergens for children.
• ... scientists have developed a nanoparticle that delivers mRNA to liver cells in order to teach the immune system to tolerate peanut protein and alleviate allergies.
• In mice, the nanoparticle successfully dampened symptoms of serious allergy.
  

... Taking inspiration from COVID-19 vaccines as well as their own research on the disease, they created a first-of-its-kind nanoparticle ... that delivers mRNA to specific cells in the liver. Those cells, in turn, teach the body’s natural defenses to tolerate peanut proteins.

In testing in mice, the nanoparticle not only reversed peanut allergies, but also prevented them from developing. ..."

From the abstract:

"While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance is the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded peanut allergen epitopes to liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting cells that induce FoxP3+ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in the dominant peanut allergen, Ara h2. These epitopes were inserted in the mRNA strand downstream of an MHC-II targeting sequence, further endowed in vitro with 5′ and 3′ capping sequences, a PolyA tail, and uridine substitution. Codon-optimized mRNA was used for microfluidics synthesis of LNPs with an ionizable cationic lipid, also decorated with a lipid-anchored mannose ligand for LSEC targeting. Biodistribution to the liver was confirmed by in vivo imaging, while ELISpot assays demonstrated an increase in IL-10-producing Tregs in the spleen. Prophylactic administration of tandem-repeat or a combination of encapsulated Ara h2 epitopes induced robust tolerogenic effects in C3H/HeJ mice, sensitized to and subsequently challenged with crude peanut allergen extract. In addition to alleviating physical manifestations of anaphylaxis, there was suppression of Th2-mediated cytokine production, IgE synthesis, and mast cell release, accompanied by increased IL-10 and TGF-β production in the peritoneum. Similar efficacy was demonstrated during LNP administration postsensitization. While nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. These results demonstrate an exciting application of mRNA/LNP for treatment of food allergen anaphylaxis, with the promise to be widely applicable to the allergy field."

Nanoparticle with mRNA appears to prevent, treat peanut allergies in mice | UCLA ... technology could provide platform to fight other allergies, autoimmune disorders

Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery (no public access)

Penicillin allergies may be linked to a single immune system gene

Good news! What a data intensive study! It seems this study has not yet even involved machine/deep learning. More to come ... 

"Around 10 percent of people say they’ve had an allergic reaction to penicillin, according to the U.S. Centers for Disease Control and Prevention. Now researchers have found a genetic link to the hypersensitivity, which, while rarely fatal, can cause hives, wheezing, arrythmias and more.  ...
That hot spot is on the major histocompatibility complex gene HLA-B [human leukocyte antigen (HLA)] ...
Several recent studies have connected distinct differences in HLA genes to bad reactions to specific drugs. For example, studies have linked an HLA-B variant to adverse reactions to an HIV/AIDS medication called abacavir, and they’ve linked a different HLA-B variant to allergic reactions to the gout medicine allopurinol. ...
For the penicillin study, the team hunted through more than 600,000 electronic health records that included genetic information for people who self-reported penicillin allergies. The researchers used several genetic search tools, which comb through DNA in search of genetic variations that may be linked to a health problem. Their search turned up a specific spot on chromosome 6, on a variant called HLA-B*55:01. ...
The group then checked its results against 1.12 million people of European ancestry in the research database of the genetic-testing company 23andMe and found the same link. A check of smaller databases including people with East Asian, Middle Eastern and African ancestries found no similar connection, although those sample sizes were too small to be sure ...

Penicillin allergies often begin in childhood, but can wane over time, making the drugs safer to use some years later, ...

The distinction matters, because about 90 percent of patients who claim to be allergic to penicillin can actually safely take the drug ..."

"... We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. ..."

Penicillin allergies may be linked to one immune system gene | Science News People with self-reported allergies to the drug may have a vulnerability on the HLA-B gene

Here is the respective research paper:

Genome-wide Study Identifies Association between HLA-B ∗ 55:01 and Self-Reported Penicillin Allergy

Fewer Infections, More Allergies: Finding the Connection

Recommendable! Could be a breakthrough!

".. they found a link between the parasitic worm that causes bilharzia – also known as snail fever, which affects more than 200 million people worldwide, mostly in Africa – and the sort of reduction in the immune response that produces allergic disorders. ... The research project was born of [the] discovery that the malaria parasite sends misleading messages to an infected person’s immune system by releasing small segments of its DNA encapsulated in sac-like “packages,” or nanovesicles. ... These findings explain how the bilharzia infection can persist for years without provoking an immune response. The findings also provide support for the hygiene hypothesis: Th2 cells are the ones mainly responsible for asthma, atopic dermatitis and various other allergic and autoimmune disorders, in which the immune system mistakenly attacks its own tissues and organs. These diseases are uncommon in developing countries where the high prevalence of parasitic infections may suppress Th2 cells."

Fewer Infections, More Allergies: Finding the Connection “Packages” released by bilharzia parasites may hold the key to better diagnosis and treatment, and may point to new ways of treating autoimmune disorders