Showing posts with label Allergies. Show all posts
Showing posts with label Allergies. Show all posts

Nov 9, 2023

Making gluten-free, sorghum-based beers easier to brew and enjoy

Though beer is a popular drink worldwide, it's usually made from barley, which leaves those with a gluten allergy or intolerance unable to enjoy the frothy beverage. Sorghum, a naturally gluten-free grain, could be an alternative, but complex preparation steps have hampered its widespread adoption by brewers. Now, researchers reporting the molecular basis behind sorghum brewing in ACS' Journal of Proteome Research have uncovered an enzyme that could improve the future of sorghum-based beers.

Traditionally, beer brewers start with barley grains, which they malt, mash, boil and ferment to create the bubbly beverage. Barley contains gluten -- a group of proteins found in several cereal grains. Sorghum, on the other hand, lacks these proteins and behaves differently than barley during brewing. For example, strong molecular bonds make it difficult to release starches from the grains during the mash stage. And fewer enzymes are present in sorghum wort -- the liquid extracted from the mashing process -- to transform the starches into simple sugars, such as glucose, which ferments into alcohol. Even when brewers adjust the reaction conditions during these steps, the resulting beverages are still less alcoholic than barley-based beers. To help bring the alcohol content up to expected standards, Edward Kerr, Glen Fox and Benjamin Schulz investigated the molecular processes that occur during sorghum brewing and found ways to improve the final product.

The team brewed both barley and sorghum beverages, taking them through malting, mashing and fermentation steps at varying temperatures and lengths of time. At the malting stage, the samples were analyzed via mass spectrometry proteomics, which revealed the presence of many of the same enzymes in barley malt and sorghum malt; those enzymes included amylases that break down starches into maltose. After the malts were steeped with water, the resulting sorghum wort contained less maltose than barley wort, but considerably more glucose. The team attributed these differences to the enzyme compositions: Sorghum wort contains fewer amylase enzymes than barley wort but more α‑glucosidase, an enzyme that breaks down starches into glucose instead. By optimizing brewing parameters to favor the activity of α‑glucosidase, the researchers say that brewers could create sorghum wort with higher concentrations of fermentable glucose, resulting in sorghum-based beers with higher alcohol content and better overall quality.

Read more at Science Daily

Aug 30, 2023

Common origin behind major childhood allergies

Several major childhood allergies may all stem from the community of bacteria living in our gut, according to a new study led by researchers at the University of British Columbia and BC Children's Hospital.

The research, published in Nature Communications, identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies -- eczema, asthma, food allergy and/or hay fever. The findings could lead to methods of predicting whether a child will develop allergies, and ways to prevent them from developing at all.

"We're seeing more and more children and families seeking help at the emergency department due to allergies," said Dr. Stuart Turvey, professor in the department of pediatrics at UBC and an investigator at BC Children's Hospital Research Institute, and co-senior author on the study. "Hundreds of millions of children worldwide suffer from allergies, including one in three children in Canada, and it's important to understand why this is happening and how it can be prevented."

The study is one of the first to examine four distinct school-aged pediatric allergies at once. While these allergic diseases each have unique symptoms, the Turvey lab was curious whether they might have a common origin linked to the infant gut microbiota composition.

"These are technically different diagnoses, each with their own list of symptoms, so most researchers tend to study them individually," says Dr. Charisse Petersen, co-senior author on the paper and postdoctoral fellow in the Turvey lab. "But when you look at what is going wrong at a cellular level, they actually have a lot in common."

For the study, researchers examined clinical assessments from 1,115 children who were tracked from birth to age five. Roughly half of the children (523) had no evidence of allergies at any time, while more than half (592) were diagnosed with one or more allergic disorders by an expert physician. The researchers evaluated the children's microbiomes from stool samples collected at clinical visits at three months and one year of age.

The stool samples revealed a bacterial signature that was associated with the children developing any of the four allergies by five years of age. The bacterial signature is a hallmark of dysbiosis, or an imbalanced gut microbiota, that likely resulted in a compromised intestinal lining and an elevated inflammatory response within the gut.

"Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action," says Courtney Hoskinson, a PhD candidate at UBC and first author on the paper. "We found a common breakdown in these mechanisms in babies prior to the development of allergies."

Many factors can shape the infant gut microbiota, including diet, how we are born, where we live, and our exposure to antibiotics. For example, antibiotics may wipe out sensitive bacteria, while breastfeeding tends to replenish and provide necessary food for bacteria in the infant gut. The researchers examined how these types of influences affected the balance of gut microbiota and the development of allergies.

"There are a lot of potential insights from this robust analysis," says Dr. Turvey. "From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied."

Now the researchers hope to leverage the findings to inform treatments that correct an imbalanced gut microbiota and could potentially prevent allergies from developing.

"Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime," says Dr. Turvey.

The research is part of the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study that recruited families through BC Children's Hospital and BC Women's Hospital + Health Centre and other pediatric hospitals across Canada. Since launching in 2008, the team of Canadian researchers has tracked the health, growth and environments of kids from birth and made important discoveries about how asthma and allergies develop.

Read more at Science Daily

May 28, 2023

Skin patch shows promise for toddlers with peanut allergy

A global phase 3 clinical trial that included Ann & Robert H. Lurie Children's Hospital of Chicago found that a year-long immunotherapy through a skin patch safely desensitized toddlers with peanut allergy, lowering the risk of a severe allergic reaction from accidental exposure. Results of this randomized, double-blind, placebo-controlled trial for children 1-3 years of age, funded by DBV Technologies, were published in the New England Journal of Medicine.

"We were excited to contribute to this landmark study that carries so much promise for our young patients with peanut allergy," said co-author Melanie Makhija, MD, who was the Principal Investigator of the study at Lurie Children's and is an Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Children who originally reacted to a small fraction of a peanut were able to tolerate the equivalent of one to four peanuts after completing the treatment course. This means that these children will be well protected from accidental exposure to peanuts. Importantly, we found that the peanut patch was safe, with very low chances of a severe allergic reaction. This is terrific news for families of kids with peanut allergies."

Peanut allergy affects approximately 2 percent of children in the United States, Canada and other westernized countries, and it commonly persists into adulthood. Life-threatening allergic reactions can be triggered by unintentional exposure to minute quantities, including through products manufactured on shared equipment as peanuts. Currently, there are no approved treatments for peanut-allergic children younger than 4 years of age.

Since 2012, the clinical trials program for food allergies at Lurie Children's has enrolled patients on numerous studies of novel treatments, including the oral immunotherapy for peanuts that has been approved by the Food and Drug Administration (FDA). Ongoing trials are available for all age groups, from infancy to young adulthood. The program is led by Principal Investigators Elizabeth Lippner, MD, and Abigail Lang, MD, MSCI.

Read more at Science Daily

Aug 6, 2022

Ragweed allergy: Aggressiveness of pollen is determined by its place of origin and by the environment

The different geographic and climatic regions from which ragweed pollen originates, as well as the degree of environmental pollution, may influence the severity of allergic reactions such as hay fever and asthma. Pollen from plants in different areas exhibit different levels of aggressiveness. This is the conclusion reached by an inter-university study team led by MedUni Vienna and involving the University of Vienna and the University of Natural Resources and Applied Life Sciences. The study was recently published in the journal Frontiers in Allergy.

The research team developed an allergy model in which mice inhaled pollen from ragweed plants (Ambrosia artemisiifolia) collected in different geographic locations. They found that even a small amount of pollen (a total of 180 pollen grains) is sufficient to produce an allergic reaction, much less than the high pollen concentrations found in the air during the seasonal flowering period. As a result of climate change, the European flowering season is getting longer, and the plant is able to spread to more northerly areas. Furthermore, the regional origin of the pollen determines the severity of the allergic reaction it produces. The lead researcher and coordinator of the "Atopica" project, Michelle Epstein from MedUni Vienna, explained: "Our study shows that pollen from distinct environments can differ in its aggressiveness. So not only the concentration of the pollen in the air but also intrinsic changes (from within) related to the environment could alter the pollen's ability to sensitise and cause more severe allergic symptoms."

Wolfram Weckwerth, Professor at the Department of Functional and Evolutionary Ecology of the University of Vienna and one of the authors, said: "We now know that environmental factors change the aggressiveness of pollen. The next steps are further characterisation of the pollen, especially at the molecular level, to unambiguously identify the mixture of allergenic components." Anke Bellaire, a collaborator at the Department of Structural and Functional Botany at the Department of Botany and Biodiversity, University of Vienna, and also one of the authors, added: "Following these exciting results, we plan to continue ultrastructural subcellular analysis of ragweed pollen for further characterisation."

Gerhard Karrer, professor of botany at the University of Natural Resources and Applied Life Sciences, who was part of the team that collected the pollen in Austria, said: "The control of ragweed is a major public health concern and an adaptation strategy for mitigating and managing the impacts of climate change."

According to the researchers, there is a high probability that climate change and other environmental factors will also affect a number of other pollen-producing plants. This applied research model now provides a strategy for further studies investigating the impacts of climate change on pollen allergy.

33 million Europeans suffer from ragweed allergy

Ragweed (Ambrosia artemisiifolia) is a highly allergenic plant whose pollen causes hay fever in sensitized people and can lead to asthma. Currently, over 33 million Europeans suffer from ragweed allergy and researchers predict an increase to 77 million cases by 2060 as a result of climate change. The EU's annual economic burden of allergic asthma is already estimated to be as much as €151 billion. Ragweed is an invasive plant that is spreading particularly rapidly in Europe in the French Rhône Valley, in northern Italy, Hungary and Croatia. The season begins in August and extends throughout autumn. However, with global warming, the season is getting longer, and warmer temperatures will encourage ragweed plants to grow in more northerly areas and at higher altitudes. A single plant can produce about a billion grains of pollen per season, and these can travel over a thousand kilometres on the wind.

Read more at Science Daily

Dec 23, 2021

Researchers lay groundwork for potential dog-allergy vaccine

There have been many research efforts describing the nature and progression of dog allergies, but there have been very few applied studies that use this information to try to cure people of dog allergies entirely by artificially inducing immune tolerance. But researchers have now for the first time identified candidates for those parts of the molecules that make up dog allergens that could give us precisely that: a "dog allergy vaccine."

Their findings were published in the Federation of European Biochemical Societies journal on October 26.

Being allergic to dogs is a common malady and one that is growing worldwide. Over the years, scientists have been able to identify seven different dog allergens -- molecules or molecular structures that bind to an antibody and produce an unusually strong immune response that would normally be harmless.

These seven are named Canis familiaris allergens 1 to 7 (Can f 1-7). But while there are seven, just one, Can f 1, is responsible for the majority (50-75 percent) of reactions in people allergic to dogs. It is found in dogs' tongue tissue, salivary glands, and their skin.

Researchers have yet to identify Can f 1's IgE epitopes -- those specific parts of the antigens that are recognized by the immune system and stimulate or 'determine' an immune response (which is why epitopes are also called antigen determinants). More specifically, epitopes are short amino acid sequences making up part of a protein that induces the immune response.

Epitopes bind to a specific antigen receptor on the surface of immune system antibodies, B cells, or T Cells, much like how the shape of a jigsaw puzzle piece fits the specific shape of another puzzle piece. (The part of the receptor that binds to the epitope is in turn called a paratope). Antibodies, also known as immunoglobulin, come in five different classes or isotypes: IgA (for immunoglobulin A), IgD, IgE, IgG, or IgM. The IgE isotype (only found in mammals) plays a key role in allergies and allergic diseases. There is also an IgE epitope that is the puzzle piece that fits the IgE isotype's paratope.

In recent years, there has been extensive effort at developing epitope-focused vaccines -- in this case, a vaccine against dog allergies.

"We want to be able to present small doses of these epitopes to the immune system to train it to deal with them, similar to the principle behind any vaccine," said Takashi Inui, a specialist in allergy research, professor at Osaka Prefecture University and a lead author of the study. "But we can't do this without first identifying the Can f 1's IgE epitope."

So the researchers used X-ray crystallography (in which the diffraction of x-rays through a material is analyzed to identify its 'crystal' structure) to determine the structure of the Can f 1 protein as a whole -- the first time this had ever been done.

They found that the protein's folding pattern is at first glance extremely similar to three other Can f allergens. However, the locations of surface electrical charges were quite different, which in turn suggest a series of 'residues' that are good candidates for the IgE epitope.

Using this basic data, further experimental work needs to be performed to narrow the candidates down, but the findings suggest the development of a hypoallergenic vaccine against Can f 1 -- a dog-allergy vaccine -- is within our grasp.

Read more at Science Daily

Sep 18, 2021

Allergies to mRNA-based COVID-19 vaccines rare, generally mild, study finds

Allergic reactions to the new mRNA-based COVID-19 vaccines are rare, typically mild and treatable, and they should not deter people from becoming vaccinated, according to research from the Stanford University School of Medicine.

The findings will be published online Sept. 17 in JAMA Network Open.

"We wanted to understand the spectrum of allergies to the new vaccines and understand what was causing them," said the study's senior author, Kari Nadeau, MD, PhD, the Naddisy Foundation Professor in Pediatric Food Allergy, Immunology, and Asthma.

The study analyzed 22 potential allergic reactions to the first 39,000 doses of Pfizer and Moderna COVID-19 vaccines given to health care providers at Stanford soon after the vaccines received emergency use authorization from the Food and Drug Administration.

Most of those in the study who developed reactions were allergic to an ingredient that helps stabilize the COVID-19 vaccines; they did not show allergies to the vaccine components that provide immunity to the SARS-CoV-2 virus. Furthermore, these allergic reactions occurred via an indirect activation of allergy pathways, which makes them easier to mitigate than many allergic responses.

"It's nice to know these reactions are manageable," said Nadeau, who directs the Sean N. Parker Center for Allergy and Asthma Research at Stanford. "Having an allergic reaction to these new vaccines is uncommon, and if it does happen, there's a way to manage it."

The study's lead author is former postdoctoral scholar Christopher Warren, PhD, now an assistant professor at Northwestern University Feinberg School of Medicine.

The research also suggests how vaccine manufacturers can reformulate the vaccines to make them less likely to trigger allergic responses, Nadeau said.

Delivery of protein-making instructions

The mRNA-based COVID-19 vaccines provide immunity via small pieces of messenger RNA that encode molecular instructions for making proteins. Because the mRNA in the vaccines is fragile, it is encased in bubbles of lipids -- fatty substances -- and sugars for stability. When the vaccine is injected into someone's arm, the mRNA can enter nearby muscle and immune cells, which then manufacture noninfectious proteins resembling those on the surface of the SARS-CoV-2 virus. The proteins trigger an immune response that allows the person's immune system to recognize and defend against the virus.

Estimated rates of severe vaccine-related anaphylaxis -- allergic reactions bad enough to require hospitalization -- are 4.7 and 2.5 cases per million doses for the Pfizer and Moderna vaccines, respectively, according to the federal Vaccine Adverse Event Reporting System. However, the federal system doesn't capture all allergic reactions to vaccines, tending to miss those that are mild or moderate.

For a more complete understanding of allergic reactions to the new vaccines -- how common they are, as well as how severe -- the research team examined the medical records of health care workers who received 38,895 doses of mRNA-based COVID-19 vaccines at Stanford Medicine between Dec. 18, 2020, and Jan. 26, 2021. The vaccinations included 31,635 doses of the Pfizer vaccine and 7,260 doses of the Moderna vaccine.

The researchers searched vaccine recipients' medical records for treatment of allergic reactions and identified which reactions were linked to the vaccines. Twenty-two recipients, 20 of them women, had possible allergic reactions, meaning specific symptoms starting within three hours of receiving the shots. The researchers looked for the following symptoms in recipients' medical records: hives; swelling of the mouth, lips, tongue or throat; shortness of breath, wheezing or chest tightness; or changes in blood pressure or loss of consciousness. Only 17 of the 22 recipients had reactions that met diagnostic criteria for an allergic reaction. Three recipients received epinephrine, usually given for stronger anaphylaxis. All 22 fully recovered.

Of the 22 recipients, 15 had physician-documented histories of prior allergic reactions, including 10 to antibiotics, nine to foods and eight to nonantibiotic medications. (Some recipients had more than one type of allergy.)

The researchers performed follow-up laboratory testing on 11 individuals to determine what type of allergic reaction they had, as well as what triggered their allergy: Was it one of the inert sugar or lipid ingredients in the bubble, or something else in the vaccine?

The study participants underwent skin-prick tests, in which a clinician injected small amounts of potential allergens -- the lipids, sugars (polyethylene glycol or polysorbates) or entire vaccine -- into the skin. Skin-prick testing detects allergic reactions mediated by a form of antibody known as immunoglobin E, or IgE; these reactions are generally associated with the severest allergies.

None of the recipients reacted on skin-prick tests to the inert ingredients in the vaccines, and just one recipient's skin reacted to the whole COVID-19 vaccine. Follow-up blood tests showed that the vaccine recipients did not have significant levels of IgE antibodies against the vaccine ingredients.

Since the skin tests did not explain the mechanism of recipients' allergic reactions, the investigators proceeded to another type of diagnostic test. Vaccine recipients provided blood samples for tests of allergic activation of immune cells known as basophils. The blood samples from 10 of the 11 participants showed a reaction to the inert ingredient polyethylene glycol (PEG), which is used in both the Pfizer and Moderna vaccines. In addition, all 11 recipients had basophil activation in response to the whole mRNA vaccine when it was mixed with their own basophils.

All 11 subjects had high levels of IgG antibodies against PEG in their blood; IgG antibodies help activate basophils under some conditions, and this finding suggests the individuals were likely sensitive to PEG before receiving their vaccines.

"What's important is what we didn't find, as much as what we did find," Nadeau said. "It does not seem that the mRNA itself causes the allergic reactions."

In addition, the data suggest that reactions to the COVID-19 vaccines were generally not the most severe form of allergic reaction, which is good news in terms of vaccine safety, she said. Allergic reactions mediated by IgG and basophils can be managed with antihistamines, fluids, corticosteroids and close observation, meaning that many individuals who have had a reaction to their first vaccine dose can safely receive a second dose under medical supervision.

PEG is widely used as a stabilizer in household products, cosmetics and medications, with women more likely to be exposed to large quantities of the substance, possibly explaining why more vaccine allergies have been seen among women. (Repeated exposures to a substance can sometimes sensitize the immune system and provoke allergies.) Because most reactions were to PEG rather than the vaccine's active ingredients, it is likely that vaccine manufacturers can reformulate the vaccines with different stabilizers that are less likely to cause allergies, Nadeau said.

Read more at Science Daily

Jul 13, 2021

More complex than we thought: The body's reaction to contact allergens

Many people react to contact allergens, but some patients develop rashes and itching much faster than others. Previously the scientists were unable to explain why, but now researchers have outlined an entire new subgroup of allergic reactions which explains these early skin reactions. The new knowledge is vital to understanding the disease mechanisms in contact allergy.

Hair dye, perfume, jewellery. Beautifying to most, but for some they are equivalent to rashes, irritation and reduced quality of life. Together with hay fever and food allergies, allergic contact dermatitis due to exposure to e.g. nickel and perfume ingredients represents the majority of allergic reactions seen among Danes.

Traditionally, researchers have distinguished between immediate and delayed allergic reactions, depending on which parts of the immune system that is responsible for the reaction. e.g., hay fever and food allergies are 'immediate' forms that cause immediate symptoms, whereas it can take days before the skin reacts to things like nickel and perfume. But now a new study conducted by the LEO Foundation Skin Immunology Research Center at the University of Copenhagen changes this understanding.

'Some patients develop allergic contact dermatitis at a much earlier stage than described by text books. The aim of the study was therefore to try to determine why some react to contact allergens much faster than prescribed. It turns out that when a part of the skin is exposed to the allergen for the first time, the cells within that specific skin area will develop local memory towards the contact allergen. And then when the same area is re-exposed to the allergen at a later point in time, the patient will develop a clear reaction within only 12 hours', explains PhD Student and first author of the study Anders Boutrup Funch.

It is the T cells in the body that are responsible for delayed allergic reactions -- also known as type 4 allergic reactions. But in the new study conducted on mice the researchers have shown that the T cells are capable of building a sophisticated memory that enables them to respond much faster than previously assumed. This gives us a more complex picture of contact allergy.

'We point to a need for clarification of this disease. Type 4 reactions should be subcategorised, giving us both the classic delayed reaction -- that is, where the patient reacts 24-72 hours after exposure -- and an immediate reaction, where the patient develops symptoms much faster. Based on these results, we may have to change the text books on contact allergy. At any case, we will need to add a chapter', says the main author of the study, Professor Charlotte Menné Bonefeld.

The study also reveals that activation of the memory T cells following exposure to an allergen leads to massive recruitment of the most abundant type of white blood cells in the body -- the so-called neutrophils -- to the affected part of the skin. Normally, neutrophil recruitment is used to fight infections, as these cells are capable of effectively eliminating microorganisms. At the same time, they cause intense infection and local tissue damage, which is what the patients experience as a rash. Neutrophil recruitment is not seen in connection with delayed reactions to contact allergens.

The next step in the research is to test the study results on humans. Once a person has developed contact allergy, they are likely to suffer from it for the rest of their lives. Therefore, the researchers behind the study hope the new knowledge may improve contact allergy patients' chances of getting treatment in the future.

Read more at Science Daily

Jun 18, 2021

First months decisive for immune system development

Many diseases caused by a dysregulated immune system, such as allergies, asthma and autoimmunity, can be traced back to events in the first few months after birth. To date, the mechanisms behind the development of the immune system have not been fully understood. Now, researchers at Karolinska Institutet show a connection between breast milk, beneficial gut bacteria and the development of the immune system. The study is published in Cell.

"A possible application of our results is a preventative method for reducing the risk of allergies, asthma and autoimmune disease later in life by helping the immune system to establish its regulatory mechanisms," says the paper's last author Petter Brodin, paediatrician and researcher at the Department of Women's and Children's Health, Karolinska Institutet. "We also believe that certain mechanisms that the study identifies can eventually lead to other types of treatment for such diseases, not just a prophylactic."

The incidence of autoimmune diseases such as asthma, type 1 diabetes and Crohn's disease is increasing in children and adolescents in parts of the world. These diseases are debilitating, but not as common in low-income countries as they are in Europe and the USA.

It has long been known that the risk of developing these diseases is largely determined by early life events; for instance, there is a correlation between the early use of antibiotics and a higher risk of asthma. It is also known that breastfeeding protects against most of these disorders.

There is a link between specific, protective bacteria on the skin and in the airways and gut and a lower risk of immunological diseases. However, there is still much to learn about how these bacteria form the immune system.

Researchers at Karolinska Institutet, Evolve Biosystems, Inc, the University of California Davis, University of Nebraska, Lincoln, and University of Nevada, Reno studied how the neonatal immune system adapts to and is shaped by the many bacteria, viruses, nutrients and other environmental factors to which the baby is exposed during the first few months of life.

Earlier research has shown that bifidobacteria are common in breastfed babies in countries with a low incidence of autoimmune diseases.

Breast milk is rich in HMOs (Human milk oligosaccharides), which babies are unable to metabolise on their own. The production of these complex sugars are instead associated with the evolutionary advantage of nourishing specific gut bacteria that play an important part in their immune system. Bifidobacteria are one such bacterial class.

"We found that babies whose intestinal flora can break down HMOs have less inflammation in the blood and gut," says professor Brodin. "This is probably because of the uniquely good ability of the bifidobacteria to break down HMOs, to expand in nursing babies and to have a beneficial effect on the developing immune system early in life."

Babies who were breastfed and received additional bifidobacteria had higher intestinal levels of the molecules ILA and Galectin-1. ILA (indole-3-lactic acid) is needed to convert HMO molecules into nutrition; Galectin-1 is central to the activation of the immune response to threats and attacks.

According to the researchers, Galectin-1 is a newly discovered and critical mechanism for preserving bacteria with beneficial, anti-inflammatory properties in the intestinal flora.

The results are based on 208 breastfed babies born at Karolinska University Hospital between 2014 and 2019. The researchers also used novel methods to analyse the immune system even from small blood samples. Additionally, a second cohort developed by the University of California in which infants were exclusively breastfed and half were fed B. infantis supplement were analyzed for enteric inflammation.

One limitation of the study is that the researchers were unable to study the immune system direct in the gut and had to resort to blood samples. Not all aspects of the gut immune system can be seen in the blood, but it is not ethically defensible to take intestinal biopsies from healthy neonates.

The researchers now hope to follow the participant babies for a longer time to see which ones develop atopic eczema, asthma and allergies.

Read more at Science Daily

Jan 28, 2021

Making wheat and peanuts less allergenic

 The United States Department of Agriculture identifies a group of "big eight" foods that causes 90% of food allergies. Among these foods are wheat and peanuts.

Sachin Rustgi, a member of the Crop Science Society of America, studies how we can use breeding to develop less allergenic varieties of these foods. Rustgi recently presented his research at the virtual 2020 ASA-CSSA-SSSA Annual Meeting.

Allergic reactions caused by wheat and peanuts can be prevented by avoiding these foods, of course. "While that sounds simple, it is difficult in practice," says Rustgi.

Avoiding wheat and peanuts means losing out on healthy food options. These two foods are nutritional powerhouses.

Wheat is a great source of energy, fiber, and vitamins. Peanuts provide proteins, good fats, vitamins and minerals.

"People with food allergies can try hard to avoid the foods, but accidental exposure to an allergen is also possible," says Rustgi. Allergen exposure can lead to hospitalization, especially for people with peanut allergies.

"For others, avoiding wheat and peanuts is not easy due to geographical, cultural, or economic reasons," explains Rustgi.

Rustgi and his colleagues are using plant breeding and genetic engineering to develop less allergenic varieties of wheat and peanuts. Their goal is to increase food options for people with allergies.

For wheat, researchers focus on a group of proteins, called gluten.

The gluten in bread flour makes dough elastic. Gluten also contributes to the chewy texture of bread.

But gluten can cause an immune reaction for individuals with Celiac disease. In addition, others experience non-celiac gluten sensitivity, leading to a variety of adverse symptoms.

Researchers have been trying to breed varieties of wheat with lower gluten content. The challenge, in part, lies in the complicated nature of gluten genetics. The information needed to make gluten is embedded in the DNA in wheat cells.

But gluten isn't a single protein -- it's a group of many different proteins. The instructions cells needed to make the individual gluten proteins are contained within different genes.

In wheat, these gluten genes are distributed all over a cell's DNA. Since so many portions of the DNA play a role in creating gluten, it is difficult for plant breeders to breed wheat varieties with lower gluten levels.

"When we started this research, a major question was whether it would be possible to work on a characteristic controlled by so many genes," says Rustgi.

For peanuts, the situation is similar. Peanuts contain 16 different proteins recognized as allergens.

"Not all peanut proteins are equally allergenic," says Rustgi. Four proteins trigger an allergic reaction in more than half of peanut sensitive individuals.

Like the gluten genes in wheat, the peanut allergen genes are spread throughout the peanut DNA.

"Affecting this many targets is not an easy task, even with current technology," says Rustgi.

Rustgi and the research team are testing many varieties of wheat and peanuts to find ones that are naturally less allergenic than others.

These low-allergenic varieties can be bred with crop varieties that have desirable traits, such as high yields or pest resistance. The goal is to develop low-allergenic wheat that can be grown commercially.

In addition to traditional breeding efforts, Rustgi is also using genetic engineering to reduce allergenic proteins in wheat and peanuts.

For example, a technology called CRISPR allows scientists to make very precise changes to a cell's DNA.

Rustgi is using CRISPR to target gluten genes in wheat. Recent improvements in CRISPR technology allow researchers to target many genes at once.

Genes targeted by CRISPR are changed or mutated. This means that cells can no longer 'read' these genes to make the specific proteins.

"Disrupting the gluten genes in wheat could yield wheat with significantly lower levels of gluten. A similar approach would work in peanuts," says Rustgi.

Other approaches include understanding how gluten production is regulated in wheat cells. As it turns out, one protein serves as a 'master regulator' for many gluten genes.

That's important because disrupting this master regulator could lead to reduced amounts of gluten in wheat. Targeting a single gene is much easier than trying to disrupt the several gluten genes.

"Wheat and peanuts are the major sources of proteins to many, especially those living in resource-deprived conditions," says Rustgi. "Finding affordable ways to make wheat and peanuts available for all is very important."

Developing wheat and peanuts with reduced allergen levels is a key step toward this goal.

Read more at Science Daily

Oct 30, 2020

Mothers pass on allergies to offspring

 Mothers can pass allergies to offspring while they are developing in the womb, researchers from the Agency for Science, Technology and Research (A*STAR), KK Women's and Children's Hospital (KKH) and Duke-NUS Medical School in Singapore reported this week in the journal Science.

The study, which employed an animal model conducted according to the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines, shows that the key antibody responsible for triggering allergic reactions, immunoglobulin E (IgE), can cross the placenta and enter the fetus. When inside the fetus, the antibody binds to fetal mast cells, a type of immune cell that releases chemicals that trigger allergic reactions, from runny noses to asthma. After birth, newborn mice develop allergic reactions to the same type of allergen as their mothers at the time of first exposure -- unlike adult mice, which require two exposures. Studies in the laboratory also showed that maternal IgE can bind to human fetal mast cells, indicating they might cross the placenta in humans in a similar way.

Dr Florent Ginhoux, Senior Principal Investigator at A*STAR's Singapore Immunology Network (SIgN), a senior co-author of the study, said, "There is currently a significant lack of knowledge on mast cells that are present early on in the developing fetus. Here, we discovered that fetal mast cells phenotypically mature through the course of pregnancy, and can be sensitised by IgE of maternal origin that cross the placental barrier. The study suggests that a highly allergic pregnant mother may potentially transfer her IgE to her baby that consequently develop allergic reactions when exposed to the first time to the allergen."

"Allergies begin very early in life," said Associate Professor Ashley St. John, an immunologist at Duke-NUS' Emerging Infectious Diseases Programme and a senior co-author of the study. "Infants experience allergic responses closely linked with the mother's allergic response in ways that cannot only be explained by genetics. This work emphasises one way that allergic responses can pass from the mother to the developing fetus, and shows how allergies can then persist after birth."

As part of the study, following NACLAR guidelines, researchers exposed mice to ragweed pollen, a common allergen, prior to pregnancy. Mice that developed a sensitivity to the pollen had offspring that also showed an allergic reaction to ragweed. The sensitivity is allergen-specific; the offspring did not react to dust mites, another common allergen.

Notably, the transfer of sensitivity appears to fade with time. The newborn mice had allergic reactions when tested at four weeks, but less or none at six weeks.

The experimental studies were backed up with cellular tests and imaging, which showed maternal IgE bound to fetal mast cells, triggering the mast cells to release chemicals in reaction to an allergen, a process called degranulation.

This study further showed that the IgE transfer across the placenta requires the help of another protein, FcRN. Mice with FcRN knocked out lacked maternal IgE attached to their mast cells, and did not develop allergies after birth.

The study findings potentially open new intervention strategies to limit such transfer to minimise the occurrence of neonatal allergies. Currently, between 10 to 30 per cent of the world's population are affected by allergies. This number is set to continue rising and a solution preventing allergies being passed from mother to child could potentially bring those numbers down over time.

"Our research has really exciting findings that may explain the high incidence of early onset atopic dermatitis (eczema) in children of mothers with clinically proven eczema, which parallel findings in our local birth cohort findings," said Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine at KKH, Senior National Medical Research Council Clinician Scientist, and Vice Chair of Research with the Obstetrics and Gynaecology Academic Clinical Programme at the SingHealth Duke-NUS Academic Medical Centre. "From a clinical point of view, developing a further understanding in placental transfer of IgE, and the mechanism of fetal mast cell activation would be key to developing strategies to reduce the chance of eczema or other allergies from being transferred from mother to baby."

Read more at Science Daily

Jul 6, 2020

Asthma and allergies more common in teens who stay up late

Teenagers who prefer to stay up late and wake later in the morning are more likely to suffer with asthma and allergies compared to those who sleep and wake earlier, according to a study published in ERJ Open Research. [1]

Asthma symptoms are known to be strongly linked to the body's internal clock, but this is the first study to look at how individual sleep preferences influence asthma risk in teenagers.

Researchers say the study reinforces the importance of sleep timing for teenagers and opens up a new channel of research in to how sleep affects teenagers' respiratory health.

The study was led by Dr Subhabrata Moitra from the division of pulmonary medicine at the University of Alberta, Canada, who carried out the research while at the Barcelona Institute for Global Health, Spain. He said: "Asthma and allergic diseases are common in children and adolescents across the world and the prevalence is increasing. We know some of the reasons for this increase, such as exposure to pollution and tobacco smoke, but we still need to find out more.

"Sleep and the 'sleep hormone' melatonin are known to influence asthma, so we wanted to see if adolescents' preference for staying up late or going to bed early could be involved in their asthma risk."

The study involved 1,684 adolescents living in West Bengal, India, aged 13 or 14 years, who were taking part in the Prevalence and Risk Factors of Asthma and Allergy-Related Diseases among Adolescents (PERFORMANCE) study.

Each participant was asked about any wheezing, asthma, or symptoms of allergic rhinitis, such as a runny nose and sneezing. They were asked a series of questions to judge whether they were 'evening types', 'morning types' or in between, such as what time of the evening or night they tend to feel tired, when they would choose to wake up, and how tired they feel first thing in the morning.

Researchers compared the teenagers' symptoms with their sleep preferences, taking into account other factors that are known to affects asthma and allergies, such as where the participants live and whether their family members smoke.

They found that the chance of having asthma was around three times higher in teens who prefer to sleep later compared to those who preferred to sleep earlier. They also found the risk of suffering allergic rhinitis was twice as high in late-sleepers compared to early-sleepers.

Dr Moitra adds: "Our results suggest there's a link between preferred sleep time, and asthma and allergies in teenagers. We can't be certain that staying up late is causing asthma, but we know that the sleep hormone melatonin is often out of sync in late-sleepers and that could, in turn, be influencing teenagers allergic response.

"We also know that children and young people are increasingly exposed to the light from mobile phone, tablets, and other devices, and staying up later at night. It could be that encouraging teenagers to put down their devices and get to bed a little earlier would help decrease the risk of asthma and allergies. That's something that we need to study more."

A second phase of the PERFORMANCE study is scheduled in 2028-29, which means it will be possible to repeat the study with a new group of teenagers to see if there has been any change in teenagers sleeping habits and their respiratory health. Dr Moitra and his team also hope to quantify their findings by taking objective measurements of participants' lung function and sleep time.

Professor Thierry Troosters is President of the European Respiratory Society and was not involved in the research. He said: "We need to know much more about why asthma and allergies are rising in children and teenager and, hopefully, find ways to reduce these conditions.

Read more at Science Daily

Jun 13, 2020

Scientists uncover immune cells that may lower airway allergy and asthma risk

The world is full of house dust mites. Do some cleaning, and you'll probably stir some up. While everyone has immune cells capable of reacting to common allergens like house dust mites, most of us have no allergic symptoms.

Still, many people do react with the typical allergic symptoms: sneezing, a runny nose, and itchy, swollen nasal passages. Others have a much more severe reaction: a life-threatening asthma attack.

To treat the root cause of allergies and asthma, researchers need to know exactly what sets these patients apart from healthy individuals.

In a new Science Immunology study, published on June 12, 2020, scientists at La Jolla Institute for Immunology (LJI) offer a clue to why non-allergic people don't have a strong reaction to house dust mites. They've uncovered a previously unknown subset of T cells that may control allergic immune reactions and asthma from ever developing in response to house dust mites -- and other possible allergens.

"We discovered new immune cell subsets and new therapeutic opportunities," says Grégory Seumois, Ph.D., instructor and director of LJI's Sequencing Core and co-leader of the new study. "This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don't develop inflammation when they breathe in allergens."

"The study highlights the power of unbiased single-cell genomics approaches to uncover novel biology," says LJI Professor Pandurangan Vijayanand, M.D. Ph.D., senior author of the new study.

The study builds on the Vijayanand lab's expertise in linking gene expression to disease development. The team also took advantage of the Immune Epitope Database, an LJI-led resource that houses information on how the immune system interacts with allergens like house dust mites.

Why house dust mites? These microscopic critters are hard to avoid, which means nearly everyone has been exposed. Even in people without a house dust mite (HDM) allergy, the immune system is likely to react in some way as it learns to recognize HDM molecules. This makes HDM a useful model for studying what causes allergies and asthma attacks.

The LJI team used a technique part of the "genomic revolution" arsenal of tools, called single-cell RNA-seq (or single cell transcriptomics) to see exactly which genes and molecules specific T cells produce in response to HDM allergens. They tested cells from four groups of people: people with asthma and HDM allergy, people with asthma but no HDM allergy, people with only HDM allergy, and healthy subjects.

Their analysis suggests that a subset of helper T cells, called interleukin (IL)-9 Th2 expressing HDM-reactive cells, is more prevalent in the blood of people with HDM-allergic asthma compared with those who are only allergic to HDM. Further analysis suggested that those IL9-TH2 cells are enriched in a group of molecules/genes that increased the cytotoxic potential of those cells. In other words, those specific T cells could kill other cells and drive inflammation.

In contrast, another subset of T cells stood out in the non-allergic subjects. These T cells express an "interferon response signature" and were enriched for a gene that encodes a protein called TRAIL. The work done by Seumois and his colleagues suggest that TRAIL could be important because it could dampen the activation of helper T cells.

This finding may mean that people with this specific cell population could have less T-cell driven inflammation in response to HDM allergens. At last, this could provide a clue to why some people develop allergies and asthma while others do not.

"Now if functional studies confirm this dampening effect, we're curious if there is a way to boost the activation of these T cells or induce their proliferation in asthmatic or allergic populations," says Seumois. "Can we act on those cells very early on, before asthma has developed?"

For example, genomics studies like this one may someday help identify children at risk of developing asthma and allergies. Early detection could open the door to preemptively acting on immune cells before development of allergy and asthma.

Read more at Science Daily

Dec 28, 2019

For restricted eaters, a place at the table but not the meal

Holiday celebrations often revolve around eating, but for those with food restrictions, that can produce an incongruous feeling when dining with friends and loved ones: loneliness.

People with restricted diets -- due to allergies, health issues or religious or cultural norms -- are more likely to feel lonely when they can't share in what others are eating, new Cornell University research shows.

"Despite being physically present with others, having a food restriction leaves people feeling left out because they are not able to take part in bonding over the meal," said Kaitlin Woolley, assistant professor of marketing in the Samuel Curtis Johnson Graduate School of Management and lead author of the research.

Across seven studies and controlled experiments, researchers found that food restrictions predicted loneliness among both children and adults.

The research also offers the first evidence, Woolley said, that having a food restriction causes increased loneliness. For example, in one experiment, assigning unrestricted individuals to experience a food restriction increased reported feelings of loneliness. That suggests such feelings are not driven by non-food issues or limited to picky eaters, Woolley said.

"We can strip that away and show that assigning someone to a restriction or not can have implications for their feeling of inclusion in the group meal," she said.

Further evidence came from a survey of observers of the Jewish holiday of Passover. When reminded during the holiday of the leavened foods they couldn't enjoy with others, participants' loneliness increased. Yet, within their own similarly restricted group, they felt a stronger bond.

Bonding over meals is an inherently social experience, Woolley notes. In previous research, she found that strangers felt more connected and trusting of each other when they shared the same food, and eating food from the same plate increased cooperation between strangers.

But when restricted from sharing in the meal, people suffer "food worries," Woolley said. They fret about what they can eat and how others might judge them for not fitting in.

Those worries generated a degree of loneliness comparable to that reported by unmarried or low-income adults, and stronger than that experienced by schoolchildren who were not native English speakers, according to the research. Compared with non-restricted individuals, having a restriction increased reported loneliness by 19%. People felt lonelier regardless of how severe their restriction was, or whether their restriction was imposed or voluntary.

The study concluded that food restrictions and loneliness are on the rise and "may be related epidemics," warranting further research.

To date, Woolley said, children have been the primary focus of research on the effects of food restrictions. A nationally representative survey she analyzed from the Centers for Disease Control did not track the issue among adults.

But increasingly, she said, food restrictions are being carried into adulthood, or adults are choosing restricted diets such as gluten-free, vegetarian and vegan for health or ethical reasons. Up to 30% of all participants in her research deal with restrictions, Woolley said.

Read more at Science Daily

Dec 20, 2019

Mowing urban lawns less intensely increases biodiversity, saves money and reduces pests

The researchers combined data across North America and Europe using a meta-analysis, a way of aggregating results from multiple studies to increase statistical strength. They found strong evidence that increased mowing intensity of urban lawns -- which included parks, roundabouts and road verges -- had negative ecological effects, particularly on invertebrate and plant diversity. Pest species, on the other hand, benefitted from intense lawn management.

"Even a modest reduction in lawn mowing frequency can bring a host of environmental benefits: increased pollinators, increased plant diversity and reduced greenhouse gas emissions. At the same time, a longer, healthier lawn makes it more resistant to pests, weeds, and drought events." said Dr Chris Watson, lead author of the study.

The issue with regular lawn mowing is that it favours grasses, which grow from that base of the plant, and low growing species like dandelion and clover. Other species that have their growing tips or flowering stems regularly removed by mowing can't compete. Allowing plant diversity in urban lawns to increase has the knock-on effect of increasing the diversity of other organisms such as pollinators and herbivores.

The effect of intense lawn mowing on pest species was the least studied aspect of the research the authors looked at, featuring in seven datasets across three studies in Eastern Canada. However, in all of these studies they found that intensive lawn mowing resulted in an increase in the abundance of weeds and lawn pests.

"These findings support a lot of research done by the turfgrass industry that shows that the more disturbance a lawn gets, the higher the likelihood of pest and weed invasion." said Dr Chris Watson.

Common ragweed, which featured prominently in the studies, is one of the most allergenic plant species found in North America and Europe. Previous studies have estimated the cost of ragweed-based allergies to be CAD$155 million per year in Quebec and €133 million a year in Austria and Bavaria. Having a more rapid reproduction than other species, ragweed is able to colonise disturbances caused by intense mowing.

Chris Watson explained that "Certain lawn invaders, such as ragweed, can be decreased simply through reducing lawn mowing frequency. This will decrease the pollen load in the air and reduce the severity of hayfever symptoms, number of people affected, and medical costs."

To understand the economic costs of intensely mowed lawns the researchers used a case study of the city of Trois-Rivières, Quebec, Canada. By using data on mowing contractor costs they estimated a 36% reduction of public maintenance costs when mowing frequency was reduced from 15 to 10 times per year in high use lawn areas and 3 times to once a year in low use areas.

"If citizens would like to see urban greenspace improvement, they have the ability to influence how governments go about this -- especially if it does not cost more money!" said Dr Chris Watson. "Likewise, complaints about long, messy lawns could quickly reduce the appetite of local government to trial these approaches -- so it's important to have some community information and education as well. We need to shake the outdated social stigma that comes from having a lawn a few centimetres longer than your neighbour's"

The potential for long grass to harbour ticks and rodents is a common concern. However, Dr Chris Watson said there is little evidence to support this. "The presence of ticks are more strongly related to host populations, like deer, than type of vegetation. With respect to small mammals, some species prefer longer grass' whereas others do not. The next phase of our research aims to explore these negative perceptions in more detail."

For their meta-analysis the researchers identified studies in an urban setting that measured mowing intensity (either height or frequency) as an experimental factor. On top of the 14 studies they identified, which took place between 2004 and 2019, they also included three previously unpublished studies from their research group. A separate case study was used to estimate the economic costs of high intensity lawn management.

On the reasons for conducting a meta-analysis, Chris Watson explained that: "Often, ecological studies are done over only one or two years and can be heavily influenced by the weather conditions during the period of study. A meta-analysis looks beyond individual years or locations to provide a broad overview of a research subject."

The number of data sources from previous studies available to the authors ultimately limited the analysis. "In this case, all studies came from North America and Europe so there is a big opportunity in seeing if the trends we found are confirmed elsewhere. Likewise, all the studies were used to explore pest species were from Eastern Canada, so it is important to do more research in other places before applying these results generally." said Dr Chris Watson.

When looking at the economic impacts of intense lawn management the authors were only able to incorporate contractor costs which included worker's salaries, equipment operation and fuel. They were unable to include the costs of pesticides and fertiliser or factor in indirect economic benefits from improved ecosystem services like pollination.

Read more at Science Daily

Sep 14, 2019

Few people with peanut allergy tolerate peanut after stopping oral immunotherapy

Allergy to peanut, which is often severe, is one of the most common food allergies in the United States. Although previous studies have shown that peanut oral immunotherapy (OIT) -- ingesting small, controlled amounts of peanut protein -- can desensitize adults and children and prevent life-threatening allergic reactions, the optimal duration and dose is unknown. In a study that followed participants after OIT successfully desensitized them to peanut, discontinuing OIT or continuing OIT at a reduced dose led to a decline in its protective effects. The study, published online today in The Lancet, also found that several blood tests administered before OIT could predict the success of therapy. The Phase 2 study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, and may inform who may benefit from peanut OIT and what changes in this experimental treatment should be implemented.

Investigators at Stanford University enrolled 120 people aged 7 to 55 with diagnosed peanut allergy in the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery, or POISED. While otherwise avoiding peanut throughout the trial, 95 participants received gradually increasing daily doses of peanut protein up to 4 grams, and 25 participants received daily placebo oat flour OIT. After 24 months, participants were given gradually increasing amounts of peanut in a controlled environment, to assess their tolerance. Of those participants who received peanut OIT, 83% passed the peanut challenge without an allergic reaction, while only 4% on placebo OIT did so.

Those on OIT who passed the challenge were then randomized to receive either placebo OIT or were switched to a 300-mg daily dose of peanut protein. One year later, more participants on 300-mg peanut OIT (37%) passed the challenge than those on placebo OIT (13%), confirming insights from smaller trials that desensitization is maintained in only a minority of participants after OIT is discontinued or reduced. Participants who passed food challenges also had lower initial levels of allergic antibodies to peanut protein and other indicators of allergic activity in the blood. Future research will focus on identifying optimal OIT regimens that maintain protection after therapy and will allow for regular food consumption without allergic symptoms.

From Science Daily

Sep 4, 2019

New peanut allergy treatment shows effectiveness and safety

People allergic to peanuts may have a new way to protect themselves from severe allergic reactions to accidental peanut exposure. It's called sublingual immunotherapy -- or SLIT -- and it involves putting a miniscule amount of liquefied peanut protein under the tongue, where it is absorbed immediately into the blood stream to desensitize the immune system to larger amounts of peanut protein.

Published in the Journal of Allergy and Clinical Immunology, the research led by first author Edwin Kim, MD, assistant professor of medicine at the UNC School of Medicine, shows that SLIT could offer patients a safe and effective way to protect themselves from severe allergic reactions or even anaphylaxis.

"As a parent of two children with nut allergies, I know the fear parents face and the need for better treatments," said Kim, member of the UNC Children's Research Institute. "We now have the first long-term data showing that sublingual immunotherapy is safe and tolerable, while offering a strong amount of protection."

There are three main immunotherapeutic ways clinician scientists have developed to treat nut allergies, and all of them attempt to desensitize the immune system to nut proteins to help patients avoid severe allergic reactions. According to Kim, about 100 mg of peanut protein can trigger a severe allergic reaction. That's the sort of trace amount people fear can show up in food "manufactured in a facility that processes peanuts." For reference, one peanut kernel contains about 300 mg.

"The main idea beyond immunotherapy is not for kids to be able to eat peanut butter and jelly sandwiches," Kim said. "It's to keep them safe from the small hidden exposures that could occur with packaged foods, at restaurants, and with other food exposures."

One immunotherapy method involves a patch on the skin that releases a small amount of peanut protein through the skin to desensitize the immune system. This approach has proved safe in clinical research but perhaps not as effective as researchers had hoped. It could become an FDA-approved treatment.

A second approach is called oral immunotherapy (OIT), which is currently under FDA review and a decision is expected this year. OIT requires patients to ingest a small portion of peanut protein daily, and over the course of time this can desensitize the immune system to accidental exposures. In a large phase 3 OIT clinical trial, patients initially ingested 0.5 mg of peanut and increased the amount to 300 mg over the course of many weeks and then maintained that 300 mg daily intake for the remainder of the year. This trial showed substantial effectiveness in protecting patients but some patients suffered serious side effects. A subsequent meta-analysis of OIT clinical trial data published in The Lancet in April suggested that more clinical research on OIT was needed due to the risk of serious side effects.

A third approach is SLIT. Instead of having patients ingest peanut protein, doctors place a small amount of peanut protein under patients' tongues, where it is immediately absorbed. Because the peanut protein avoids digestion, patients are given much less peanut protein -- about 0.0002 mg initially. This amount then increases over the course of months to just 2 mg.

In 2011, Kim and colleagues -- including Wesley Burks, MD, dean of the UNC School of Medicine -- conducted a small study of 18 patients to show that SLIT was safe and effective over the course of one year. Since then, Kim and colleagues followed 48 patients in the SLIT protocol of 2 mg daily for five years. In the JACI paper, the researchers showed that 67 percent of these patients were able to tolerate at least 750 mg of peanut protein without serious side effects. About 25 percent could tolerate 5000 mg.

Kim's data shows SLIT was about as effective as OIT, though the SLIT study was much smaller. And SLIT posed much less risk of serious side effects. The most common side effect was itchiness around the mouth that lasted about 15 minutes and did not need treatment. No one left the multi-year study because of side effects.

"SLIT participants tolerated between 10 and 20 times more peanut protein than it would take for someone to get sick," Kim said. "We think this provides a good cushion of protection -- maybe not quite as good as OIT -- but with an easier mechanism (sublingually) and, as far as we can tell right now, a better safety signal."

Kim's lab has finished a separate SLIT study of 4 mg daily for 55 patients over the course of four years. He hopes to publish results later this year. "With sublingual immunotherapy, we hope we can maintain our safety profile while seeing an even stronger benefit for patients," Kim said.

Read more at Science Daily

Jul 16, 2019

Australian bee sting vaccine trial holds promise against allergic reactions

Most people have probably been stung by a bee and while it can be painful, it's especially dangerous for the many that are at risk of suffering a life threatening allergic reaction.

Australian researchers have successfully completed a human trial on a vaccine designed to eliminate the risk of a severe allergic reaction to European honeybee stings.

The clinical trial at Flinders University and the Royal Adelaide Hospital included 27 adults with a history of allergic reactions to bee stings.

The vaccine used in the trial contained a unique sugar-based ingredient called an adjuvant, developed in Australia, which is designed to help the body neutralise the bee venom at a faster rate.

Professor Nikolai Petrovsky says the adjuvant used to enhance the bee sting vaccines has now been successfully given to over a thousand individuals across a range of different vaccines including in the current bee sting allergy trial.

"Our technology is like adding a turbocharger to a car and in this case makes the bee allergy vaccine much more powerful, allowing the immune system to better neutralise the bee venom and prevent allergic symptoms," says Professor Petrovsky.

Associate Professor Robert Heddle, lead investigator in the trial, says the aim was to see if the Advax adjuvant would safely speed up and improve bee sting immunotherapy.

"The results of the study were very promising and confirmed the safety of this approach to improving bee sting immunotherapy."

Dr Anthony Smith, an investigator in the trial, says while a commercial bee venom therapy is already available, it requires patients to have over 50 injections over a 3 year period to build up their immune system.

"The current treatment option for serious bee venom allergies is lengthy and cumbersome, so I hope this enhanced bee venom therapy brings about faster, but longer lasting protection to bee stings for allergic individuals."

The Advax adjuvant which enhances the bee sting vaccines was developed in Adelaide by Vaxine Pty Ltd and has also been used to develop vaccines for seasonal and pandemic influenza, hepatitis, malaria, Alzheimers disease, cancer and other diseases.

From Science Daily

Jan 5, 2019

One in 10 adults in US has food allergy, but nearly 1 in 5 think they do

Over 10 percent of adults in the U.S. -- over 26 million -- are estimated to have food allergy, according to a study published in JAMA Network Open that was led by Ruchi Gupta, MD, MPH, from Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University. However, researchers found that 19 percent of adults think they are currently food allergic, although their reported symptoms are inconsistent with a true food allergy, which can trigger a life-threatening reaction. Results are based on a nationally representative survey of over 40,000 adults.

"While we found that one in 10 adults have food allergy, nearly twice as many adults think that they are allergic to foods, while their symptoms may suggest food intolerance or other food related conditions," says lead author Ruchi Gupta, MD, MPH, from Lurie Children's, who also is a Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "It is important to see a physician for appropriate testing and diagnosis before completely eliminating foods from the diet. If food allergy is confirmed, understanding the management is also critical, including recognizing symptoms of anaphylaxis and how and when to use epinephrine."

Researchers discovered that only half of adults with convincing food allergy had a physician-confirmed diagnosis, and less than 25 percent reported a current epinephrine prescription.

Researchers also found that nearly half of food-allergic adults developed at least one of their food allergies as an adult.

"We were surprised to find that adult-onset food allergies were so common," says Dr. Gupta. "More research is needed to understand why this is occurring and how we might prevent it."

The study data indicate that the most prevalent food allergens among U.S. adults are shellfish (affecting 7.2 million adults), milk (4.7 million), peanut (4.5 million), tree nut (3 million), fin fish (2.2 million), egg (2 million), wheat (2 million), soy (1.5 million), and sesame (.5 million).

Read more at Science Daily

Nov 19, 2018

New treatment to protect people with peanut allergies ready for FDA review

The final research results for a new treatment for protection against accidental exposure to peanut was presented today at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting and published in the New England Journal of Medicine. The results show it is possible for some people with peanut allergy to protect themselves from accidental ingestion by building up their tolerance to peanut over time.

"We're excited about the potential to help children and adolescents with peanut allergy protect themselves against accidentally eating a food with peanut in it," says allergist Stephen Tilles, MD, ACAAI past president, study co-author, and consulting advisor for Aimmune Therapeutics. "Our hope when we started the study was that by treating patients with the equivalent of one peanut per day, many would tolerate as much as two peanuts. We were pleased to find that two thirds of the people in the study were able to tolerate the equivalent of two peanuts per day after nine to 12 months of treatment, and half the patients tolerated the equivalent of four peanuts."

Study participants ranged in age from 4 to 55 years, most were 4 to 17, and all had peanut allergy. One third of the participants were given a placebo, while the remaining two-thirds were given peanut protein powder in increasing amounts until reaching the "maintenance dose" -- the dose they stayed on for the remainder of the study. The maintenance does was the equivalent of one peanut daily.

"This is not a quick fix, and it doesn't mean people with peanut allergy will be able to eat peanuts whenever they want," says allergist Jay Lieberman, MD, vice chair of the ACAAI Food Allergy Committee and study co-author. "But it is definitely a breakthrough. The hope would be to have a treatment available in the second half of 2019. If that happens, people who receive and are able to tolerate this treatment should be protected from accidental exposures."

All those in the study received peanut protein as part of an oral food challenge (OFC). A person in an OFC is given a very small dose of the food by mouth under the supervision of a board-certified allergist to test for a severe reaction. OFCs are considered the gold standard for testing food allergy.

"Reactions from the oral challenges at the end of the study were much milder than prior to treatment," says Dr. Tilles. "On average, the participants were able to tolerate a 100-fold higher dose of peanut at the end of the study than they did at the beginning. In addition, the symptoms caused by the 100-fold higher dose at the end of study were milder than the symptoms on the lower dose at the beginning of the study."

Facts about this pivotal study:

  • More participants and more detailed data than all prior oral immunotherapy studies combined
  • Fewer severe allergic reactions requiring epinephrine during oral food challenges
  • Fewer side effects than anticipated -- e.g. only six percent dropped out of the study due to gastrointestinal side effects; Also, one-third of patients completed the study with no more than mild side effects along the way.
  • 80 percent of participants successfully reached daily maintenance dose of the equivalent of one peanut.
Read more at Science Daily