Category: Allergies

Categories : Allergies PaediatricsTags :

Common Gut Microbiota Link to the Development of Childhood Allergies

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Several major childhood allergies may all stem from the gut microbiome gut, according to a new study published in Nature Communications. The research identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies. The study, led by researchers at the University of British Columbia and BC Children’s Hospital, could lead to methods of predicting whether a child will develop allergies, and methods to prevent their development.

“We’re seeing more and more children and families seeking help at the emergency department due to allergies,” said Dr Stuart Turvey, paediatrics professor at UBC and co-senior author on the study, noting that as many as one in three children in Canada have allergies.

The study is one of the first to examine four distinct school-aged paediatric allergies at once: atopic dermatitis, asthma, food allergy and allergic rhinitis. 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 1115 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, place and delivery method of birth and antibiotics exposure. 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.

Source: University of British Columbia

Categories : Allergies PaediatricsTags :

Food Allergy in Infancy Linked to Childhood Asthma and Reduced Lung Function

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Infants that have a food allergy have an increased risk of asthma and reduced lung function later in childhood, according to a world first study published in the Lancet Child & Adolescent Health.

Food allergy affects 10% of babies and 5% of children and adolescents. The research, led by Murdoch Children’s Research Institute, found that early life food allergy was associated with an increased risk of both asthma and reduced lung growth at six years of age.

Murdoch Children’s Associate Professor Rachel Peters said this was the first study to examine the relationship between challenge-confirmed food allergy in infancy and asthma and poorer lung health later in childhood.

The Melbourne research involved 5276 infants from the HealthNuts study, who underwent skin prick testing to common food allergens, such as peanut and egg, and oral food challenges. At six years, children were followed up with further food allergy and lung function tests.

The study found by six years of age, 13.7% reported a diagnosis of asthma. Babies with a food allergy were almost four times more likely to develop asthma at six years of age, compared to children without a food allergy. The impact was greatest in children whose food allergy persisted to age six as opposed to those who had outgrown their allergy. Children with a food allergy were also more likely to have reduced lung function.

Associate Professor Peters said food allergy in infancy, whether it resolved or not, was linked to poorer respiratory outcomes in children.

“This association is concerning given reduced lung growth in childhood is associated with health problems in adulthood including respiratory and heart conditions,” she said.

“Lung development is related to a child’s height and weight and children with a food allergy can be shorter and lighter compared to their peers without an allergy. This could explain the link between food allergy and lung function. There are also similar immune responses involved in the development of both food allergy and asthma.

“The growth of infants with food allergy should be monitored. We encourage children who are avoiding foods because of their allergy to be under the care of a dietician so that nutrition can be catered for to ensure healthy growth.”

Source: Murdoch Childrens Research Institute

Categories : Allergies AntibioticsTags :

Most Penicillin Allergy Labels are Unnecessary – Here’s How to Fix That

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Penicillin allergy affects up to 1 in 10 Americans yet most penicillin allergy labels are in fact incorrectly applied. In addition to limiting the choice of antibiotics to prescribe, the widespread mislabelling contributes to the growing threat of antibiotic resistance. A new procedure developed by researchers at Vanderbilt University Medical Center aims to fix that.

Some 75% of penicillin allergy labels come on by age 3 due to, for example, confusion with a viral rash. The majority of these rashes were never allergic, but the labels ‘stick’ into adulthood and carry many adverse consequences.

Many low-risk patients with a penicillin allergy were able to have their penicillin allergy label removed through a simple procedure known as “direct oral challenge” as part of a world-first multi-centre randomised control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) study, the results of which were published in JAMA Internal Medicine.

In the PALACE study, investigators randomised low-risk penicillin allergic patients to two different approaches to remove their allergy label. They either underwent the current standard of care to have skin testing followed if negative by oral challenge with a penicillin or they went straight to oral challenge (“direct oral challenge”) without preceding skin testing.

“The majority of patients labelled as penicillin allergic, more than 90%, have low-risk histories, meaning they did not have a history to suggest a severe or more recent reaction to a penicillin,” said PALACE study protocol member and Vanderbilt University Medical Center principal investigator Elizabeth Phillips, MD. “We would expect more than 95% of these patients to have negative testing and be able to take penicillin in the future.”

The study, undertaken by a team of researchers from specialised centres in North America and Australia, enrolled 382 adults who were assessed using a specialized risk assessment tool called PEN-FAST. Participants were randomly assigned to receive either a direct oral penicillin challenge or the standard approach (penicillin skin testing followed by an oral challenge). The primary goal was to determine if the direct oral penicillin challenge was no worse than the standard method of skin testing followed by oral challenge which needs to be performed in an allergist’s office.

Only one patient (0.5%) in each group experienced a positive reaction to the penicillin challenge, demonstrating that the direct oral penicillin challenge performs just as well as the standard method. Importantly, there were no significant differences in adverse events between the two groups, and no serious adverse events were reported.

The findings have wide-ranging implications for patients. By accurately identifying low-risk penicillin allergy patients, health care providers can ensure appropriate antibiotic prescriptions. Patients with a documented penicillin allergy are more likely to be prescribed alternative antibiotics, known as second-line antibiotics, which are often not as effective against certain infections and may have more side effects.

“Patients with penicillin allergy are more likely to get second-line or broader spectrum antibiotics that lead to risk of antibiotic resistance and serious infections such as antibiotic-associated diarrhoea due to Clostridioides difficile, which can spread through hospitals and become a major public health problem.” Phillips said. “In the US increasingly we also have a major problem with other antibiotic-resistant ‘superbugs’ such as multi-resistant gram-negative infections, Candida auris and even a resurgence of syphilis for which penicillin is the best treatment and the only treatment that should be used in pregnancy to prevent transmission to an unborn child.

“The evidence provided by the PALACE study will change clinical practice. Many patients in the United States do not have direct access to an allergist to provide specialised testing such as skin testing. Therefore, the ability to go to direct oral challenge with a penicillin in low-risk patients which can be carried out in any observed setting will make it easier for patients in the United States to access health care to safely and effectively remove the label of penicillin allergy,” she said.

Source: Vanderbilt University Medical Center

Categories : Allergies Immune SystemTags :

Mast Cells Instruct the Brain to Avoid Allergens

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Mast cells functions are still something of a mystery, but scientists have now shown in mice that mast cells act as a sensor that signals the animals to avoid antigens, including harmful allergens, and thereby protect themselves from health-threatening inflammatory reactions. The findings were published in the journal Nature.

Mast cells are found primarily in tissues that separate the outside and inside worlds of the body, such as the epithelia of the gastrointestinal tract and lungs. Within the tissues, mast cells often reside near nerve endings. Mast cells are well known to persons suffering from allergies because they secrete messenger substances such as histamine, which cause annoying to health-threatening allergic symptoms. These symptoms occur when mast cells are activated by IgE class antibodies during repeated antigen contact.

“Why mast cells and IgE exist at all has not yet been conclusively explained,” says immunologist Hans-Reimer Rodewald at the at the German Cancer Research Center (DKFZ). The researcher his team have now been able to show for the first time in mice, in a combination of behavioural experiments and immunological studies, that mast cells act like a sensor that helps to avoid contact with allergens

Mast cells and IgE needed for antigen avoidance

The DKFZ researchers immunised mice with the allergen ovalbumin, a protein component of chicken egg white. They then gave the animals the free choice of preferring either normal or egg white-containing drinking water. Immunised animals avoided the egg white-enriched water, while their non-immunised conspecifics clearly preferred it. A large proportion of the immunised animals avoided the egg white-containing water already one day after immunisation, some mice even after the first sip.

However, when the scientists performed this behavioural test with mice that genetically lack mast cells, both immunised and non-immunised animals preferred the egg white-containing water. Mice genetically unable to produce IgE also showed no avoidance behaviour. Thus, both mast cells and IgE are responsible for antigen avoidance.

When the immunised mice had no choice because the egg white solution was instilled in them, the animals developed inflammation in the stomach and small intestine. “The avoidance behaviour mediated by mast cells apparently protects the animals from harmful immune reactions,” explains Thomas Plum, one of the first authors.

How do mast cells “talk” to the brain?

An important open question for the scientists was now: How can mast cells, as a component of the immune system, influence behaviour? In what ways do immune cells “talk” to the brain? The scientists examined a variety of biologically active substances released by mast cells. These include leukotrienes, pro-inflammatory messengers known to activate sensory nerves. If the researchers blocked leukotriene synthesis, the immunized mice no longer showed the same consequence in avoiding egg white. Leukotrienes therefore appear to be at least partly involved in avoidance behaviour. Further immunological and neurobiological experiments are needed in the future to identify the nerve connections through which the mast cell signal is reported to the brain.

“In the intestine, lungs or skin, immune reactions against non-infectious antigens can occur as a result of so-called barrier disorders, permeability of the tissues from the outside to the inside. In the case of allergy, we call such antigens allergens. Whether these substances are dangerous or not, it is important for the organism to avoid their further intake in order to prevent inflammatory diseases. This is an evolutionary advantage and finally a conclusive explanation of the physiological role of mast cells and IgE,” Rodewald summarizes the results.

Whether mast cells also contribute to the avoidance of harmful antigens in humans must be addressed in further studies.

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Categories : AllergiesTags :

Rare T Cell Could Guide Precision Treatment of Allergies

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In a new Nature Immunology study, researchers sheds light on how a rare type of helper T cell, called Th9, can drive allergic disease, suggesting new precision medicine approaches to treating allergies in patients with high levels of Th9.

“Th9 cells are kind of like the black sheep of helper T cells,” said senior author Daniella Schwartz, MD, assistant professor of rheumatology at Pitt’s School of Medicine. “They need a perfect storm of occurrences to pop up, and they aren’t long-lived, which makes them hard to study. The other weird thing about Th9 cells is that they remain functional without seeing their antigen.”

T cells switch on when they encounter viruses, bacteria or other pathogens, causing them to ramp up production of inflammatory proteins called cytokines, which control a suite of immune responses via the JAK-STAT signalling pathway. The main “on” switch for T cells is when the T cell receptor recognises an antigen, a specific identifying feature of a threat. Beyond this specific form of activation, there’s also another type of switch known as bystander activation, which doesn’t involve the T cell receptor.

“Bystander activation usually requires other types of dangerous signals that indicate a threat,” said Schwartz. “What’s really unusual about Th9 cells is that they can be turned on even without these dangerous signals.”

To learn more about how Th9 cells are activated in allergic responses, the team measured the cytokine IL9, produced by Th9 cells, in T cells from patients with atopic dermatitis, and healthy volunteers. They found that Th9 cells from the allergy patients responded to bystander activation, but not those from healthy volunteers.

“This told us that there’s some sort of checkpoint that prevents non-specific activation of Th9 cells in healthy people,” explained Schwartz. “In allergy patients, we hypothesised that the checkpoint breaks down, so you’re getting production of the cytokine even without restimulating the cells with antigen.”

In most helper T cells, when antigen binds to T cell receptor, this highly specific recognition process causes DNA in the T cell’s nucleus to unwind like thread on a spool, opening up regions of DNA that encode the production of cytokines that unleash a suite of immune responses. When the threat is eliminated, there’s no more antigen to stimulate T cell receptors and the cells turn off. But the DNA structure remains open so that the cell is poised for a possible future encounter.

Schwartz and her team found that Th9 cells have a different type of regulation. These cells are activated by transcription factors called STAT5 and STAT6, which bind to the open region DNA around IL9 to activate the gene. Unusually, the DNA closes over time, shutting down production of IL9.

In healthy people, this opening and closing mechanism acts like a checkpoint to manage immune responses being on all the time. But when this checkpoint breaks down in allergy, the DNA remains open, keeping the IL9 gene switched on and driving allergic inflammation.

In a mouse model of allergic asthma driven by Th9, blocking JAK-STAT signaling with a drug called tofacitinib, which is approved for treating rheumatoid arthritis, atopic dermatitis and other inflammatory disorders, improved disease symptoms

Analysing data from allergic asthma patients, the researchers found that those with higher levels of Th9 cells had greater activation of STAT5 and STAT6-related genes. This finding supports the idea that Th9 could act as a biomarker to predict patients who are likely to respond to JAK inhibitors, pointing to new approaches for allergy precision medicine.

Source: University of Pittsburgh

Categories : AllergiesTags :

BP and Temperature Drop in Anaphylaxis Could be due to Nervous System

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Anaphylactic shock can occur in response to food allergies or bites from insects or venomous animals. A key feature of this severe allergic reaction is an abrupt drop in blood pressure and body temperature, causing fainting and, if left untreated, potentially death.

That response has long been attributed to a sudden dilation and leakage of blood vessels. Duke Health researchers have found that this response, especially body temperature drop, requires an additional mechanism: the nervous system.

Published in the journal Science Immunology, the mouse-based study could point to new targets for therapies to prevent or treat anaphylactic shock. “This finding for the first time identifies the nervous system as a key player in the anaphylactic response,” said senior author Soman Abraham, PhD, professor at Duke University School of Medicine.

“The sensory nerves involved in thermal regulation – especially the nerves that sense high environmental temperatures – send the brain a false signal during anaphylaxis that the body is exposed to high temperatures even though it is not the case,” Abraham said. “This causes a rapid drop in body temperature as well as blood pressure.”

Abraham and colleagues, including first author Chunjing “Evangeline” Bao, a Ph.D. candidate in Abraham’s lab at Duke, tracked the sequence of events when allergens activate mast cells — the immune cells that trigger the chemical reactions leading to swelling, difficulty breathing, itchiness, low blood pressure and hypothermia.

The researchers found that one of the chemicals mast cells unleash when they are activated is an enzyme that interacts with sensory neurons, notably those involved in the body’s thermoregulatory neural network.

When stimulated as part of an allergic reaction, this neural network gets the signal to immediately shut down the body’s heat generators in the brown fat tissue, causing hypothermia. The activation of this network also causes a sudden drop in blood pressure.

The researchers validated their findings by showing that depriving mice of the specific mast cell enzyme protected them against hypothermia, whereas directly activating the heat sensing neurons in mice induced anaphylactic reactions such as hypothermia and hypotension.

“By demonstrating that the nervous system is a key player – not just the immune cells – we now have potential targets for prevention or therapy,” Bao said. “This finding could also be important for other conditions, including septic shock, and we are undertaking those studies.”

Source: Duke University Medical Center

Categories : AllergiesTags :

For Eosinophilic Oesophagitis, Cutting out Milk is as Effective as More Restrictive Diet

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Eliminating animal milk alone from the diet of adults with eosinophilic oesophagitis (EoE) is as effective at treating the disease as eliminating animal milk plus five other common foods, according to a clinical trial published in The Lancet Gastroenterology & Hepatology. For people with EoE whose disease remains active after they cut out animal milk, a more restrictive diet may help them achieve remission, according to the researchers.

“Diet-based therapy for eosinophilic esophagitis will be much easier to follow for many people if it involves cutting just one food from the diet rather than six,” said Hugh Auchincloss, M.D., acting director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.

EoE is a chronic disease characterised by an overabundance of white blood cells called eosinophils in the pesophagus. Food allergy inflammation drives the disease by damaging the oesophagus and preventing it from working properly. For people with EoE, swallowing even small amounts of food can be a painful and stressful choking experience.

Excluding certain foods from the diet has been a cornerstone of EoE treatment. During the early 2000s, researchers found that eliminating six common food triggers of oesophageal injury (milk, egg, wheat, soy, fish and nuts) substantially reduced signs and symptoms of EoE. This six-food elimination diet (6FED) became a common approach to managing the disease.

In recent years, scientists have conducted small, non-randomised studies of removing one to four of the most common food antigens from the diet to treat EoE, with some success. However, the relative risks and benefits of eliminating many foods versus a few foods at the start of diet-based therapy remained unclear.

The multi-site, randomised trial involved 129 adults ages 18 to 60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in oesophageal tissue. Participants were randomised to either the 1FED, which eliminated only animal milk from the diet, or the 6FED. They followed their assigned diet for six weeks, then underwent an upper endoscopy exam and an oesophageal tissue biopsy. If the number of eosinophils in the tissue indicated that EoE was in remission, the participant exited the study. If EoE was not in remission, people who had been on 1FED could advance to 6FED, and people who had been on 6FED could take topical swallowed steroids, both for six weeks, followed by a repeat exam with tissue biopsy.

The investigators found that 34% of participants on 6FED and 40% of participants on 1FED achieved remission after six weeks of diet therapy, a difference that was not statistically significant. The two diets also had a similar impact across several other measures, including reduction in EoE symptoms and effect on quality of life. Thus, 1FED and 6FED were equally effective at treating EoE, an unexpected finding.

The researchers also discovered that nearly half of people who did not respond to 1FED attained remission after treatment with the more restrictive 6FED, while more than 80% of the non-responders to 6FED achieved remission with oral steroids.

Taken together, the investigators conclude that 1FED is a reasonable first-line diet therapy option in adults with EoE, and that effective therapies are available for people who do not achieve remission after 1FED or 6FED.

Source: NIH/National Institute of Allergy and Infectious Diseases

Categories : AllergiesTags :

A Regimen of Boiled Peanuts Desensitises Allergy Sufferers

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Researchers took advantage of the fact that heat can affect the structure and immunoreactivity of peanuts, and tested out a peanut allergy therapy for children using sequential doses of boiled peanuts followed by roasted peanuts. Their trial, which is published in Clinical & Experimental Allergy, generated promising results, with 80% of participants experiencing desensitisation.

For this open-label, phase 2, single-arm clinical trial, 70 children aged 6–18 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily.

Fifty-six of the 70 (80%) participants became desensitised to peanuts. Treatment-related adverse events were reported in 43 (61%) participants, of whom three withdrew from the trial.

“Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitisation and is associated with a favourable safety profile,” the authors wrote.

Source: Wiley

Categories : Allergies PaediatricsTags :

IgA Antibodies Do not Prevent Childhood Food Allergies

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The presence of food-specific IgA antibodies in the gut does not prevent peanut or egg allergies from developing in children, according to a Northwestern Medicine study published in Science Translational Medicine.

Scientists examined stool samples from more than 500 infants across the country and found that the presence of Immunoglobulin A, the most common antibody found in mucous membranes in the digestive tract, does not prevent peanut or egg allergies from developing later in life.

This discovery calls into question the role of Immunoglobulin A, or IgA, which was previously thought to be a protective factor against the development of food allergies.

Peanuts and eggs are the two most common allergens for infants and affect an estimated one in 13 children in the US, according to the Ann & Robert H. Lurie Children’s Hospital of Chicago.

While prior research had shown IgA could bind to and neutralide toxins and bacteria in the body, there was inconclusive evidence that IgA could do the same for food allergens, said Stephanie Eisenbarth, MD, PhD, senior author of the study.

“We were able to collaborate with different groups around the country to look at a number of different cohorts of children and young adults to ask: ‘Does the presence of IgA to peanut tell us that the person is tolerant to peanut?’,” said Eisenbarth. “We found that there really was no difference between kids who had peanut allergies and children who didn’t, and the same is true with egg allergies.”

The findings come as rates of allergies in children continue to climb: According to data from the Centers for Disease Control and Prevention, the number of children with allergies has more than doubled in the last 20 years.

Future directions for research will center on understanding the role IgA plays in people who have undergone immunotherapy and developed a tolerance to food allergens, Eisenbarth said.

Source: Northwestern University

Categories : AllergiesTags :

Smartphones are Potential Reservoirs for Allergens

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Smartphones are nowadays ubiquitous and repeatedly checked throughout the day, making them potential receptacles for environmental hazards such as allergens. A new study being presented at this year’s American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting in Louisville, KY, showed elevated levels of cat and dog allergens, as well as β-D glucans (BDG) and endotoxin on simulated phone models.

“Smartphones showed elevated and variable levels of BDG and endotoxin, and cat and dog allergens were found on smartphones of pet owners” says Hana Ruran, lead author on the study. “BDGs are found in fungal cell walls and have been found in many environments and surfaces causing chronic airway and irritant symptoms – making BDGs a consistent marker to study problematic mould. Endotoxin is a potent inflammatory agent and a marker of exposure to Gram negative bacteria.”

The researchers created phone models that had a similar size and surface to a real phone and the front surface of the phone model was wiped as part of the test. Electrostatic wipes (ESW) were used to sample simulated phone models of 15 volunteers and the “phones” were then measured for allergens, BDG and endotoxin levels.

The chemicals used in the mixture solutions for cleaning (chlorhexidine, cetylpyridinium chloride, tannic acid and benzyl benzoate) can be purchased through laboratory or chemical suppliers but are not commercially available in the same concentrations as used in the study. Isopropyl alcohol wipes were also tested for their cleaning properties.

“Combination chlorhexidine/cetylpyridinium was the most effective in reducing BDG and endotoxin and combination benzyl benzoate/tannic acid most effectively reduced cat and dog allergens on smartphones,” says Peter Thorne, PhD, professor in the University of Iowa Department of Public Health and co-author of the study. “The study demonstrates exposure to inhalant allergens and molecules that trigger innate immune reactions from a source most people haven’t considered. If you have allergies or asthma, you may want to think about cleaning your smartphone more often to minimise exposure to these allergens and asthma triggers.”

Source: American College of Allergy, Asthma, and Immunology