Category: Allergies

Categories : Allergies PaediatricsTags :

The Process of Remission from Peanut Allergy Mapped Out

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Credit: NIH

An Australian study published in Allergy, has identified the key immunological changes that support the remission of peanut allergy in children, a discovery that could pave the way to new, more targeted treatments.

The research showed, for the first-time, that specific gene networks are rewired to drive the transition from peanut allergy to clinical remission following a combination treatment of a probiotic and peanut oral immunotherapy.

The study found that this network reprogramming essentially shuts down the allergic immune response that was responsible for causing a food allergy.

Lead researcher, Professor Mimi Tang of Murdoch Children’s Research Institute, said this was the first study to map the complex gene to gene communication and connectivity underlying clinical remission of peanut allergy.

“The immunological changes leading to remission of peanut allergy were largely unknown,” she said. Previous studies had mostly focused on examining the levels of gene expression, without also exploring how genes interact with each other. But genes don’t work in isolation; instead, biological responses are controlled by large numbers of genes communicating with each other, so it made sense to look at these interactions more closely.

“What we found was profound differences in network connectivity patterns between children who were allergic and those who were in remission. These same changes were also seen when we compared gene networks before and after immunotherapy in the children who achieved remission following immunotherapy.”

The randomised controlled trial involved 62 peanut allergic children, ages 1–10, who received a combination treatment of a probiotic and oral immunotherapy (gradual introduction of the allergen) or a placebo. Following 18 months of treatment, 74% taking the combination treatment achieved remission compared with 4% in the placebo group.

The peanut oral immunotherapy that was used in combination with the probiotic in the trial was PRT120, a lead candidate from biotech company Prota Therapeutics.

The team led by Professor Tang also recently showed in a separate trial that two treatments — the combination probiotic and peanut oral immunotherapy treatment and the peanut oral immunotherapy alone — were highly effective at inducing remission and desensitisation. About half of the treated children achieved remission, which allowed them to stop treatment and safely eat peanut freely.

Murdoch Children’s Dr Sarah Ashley said while oral immunotherapy could successfully induce desensitisation and remission, desensitisation often waned after treatment ended or even during ongoing maintenance dosing.

“Certain changes in the allergen-specific immune cells, called Th2 cells, are critical to achieving lasting remission,” she said. Th2 cells are essential for generating allergen-specific antibodies and the development of food allergy. We found that the Th2 signalling that drives allergy is ‘turned off’ in children in remission.”

Food allergy is a global public health concern, affecting 10% of infants and 5–8% of children.

Source: Murdoch Children’s Research Institute

Categories : Allergies Obstetrics & GynaecologyTags :

No Food Allergy Link to Caesarean Delivery

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Man holding newborn baby
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A new study found that caesarean delivery, either with or without labour, or elective or emergency, compared to vaginal birth does not impact on the likelihood of food allergy at 12 months of age. Led by the Murdoch Children’s Research Institute (MCRI), the study was published in the Journal of Allergy and Clinical Immunology: In Practice.

Associate Professor Rachel Peters of the Children’s Research Institute (MCRI) said the association between food allergy and mode of delivery remained unclear due to the lack of studies with food challenge outcomes.

The study involved 2045 infants from the HealthNuts study, with data linked to a perinatal database for detailed information on birth factors.

The study found that, of the 30% born by caesarean, 12.7% had a food allergy compared to 13.2% born vaginally.

“We found no meaningful differences in food allergy for infants born by caesarean delivery compared to those born by vaginal delivery,” Associate Professor Peters said. “Additionally, there was no difference in the likelihood of food allergy if the caesarean was performed before or after the onset of labour, or whether it was an emergency or elective caesarean.”

Associate Professor Peters said it was thought a potential link between caesarean birth and allergy could reflect differences in early microbial exposure from the mother’s vagina during delivery.

“The infant immune system undergoes rapid development during the neonatal period,” she said. Caesarean delivery may interfere with the normal development of the immune system, as there is less exposure to the mother’s vagina and gut bacteria, influencing the baby’s own microbiome. “However, this doesn’t appear to play a major role in the development of food allergy.”

Australia has the highest rates of childhood food allergy in the world, with about one in 10 infants and one in 20 children over five years of age having a food allergy.

These findings come as other MCRI-led research found 30% of peanut allergy and 90% of egg allergy resolves naturally by age six.

Associate Professor Peters said the resolution rates were great news for families and were even a little higher than what was previously thought.

The results, published in the Journal of Allergy and Clinical Immunology, found infants with early-onset and severe eczema and multiple allergies were less likely to outgrow their egg and peanut allergies.

Associate Professor Peters said these infants should be targeted for early intervention trials that evaluate new treatments for food allergy such as oral immunotherapy.

“Prioritising research of these and future interventions for infants less likely to naturally outgrow their allergy would yield the most benefit for healthcare resources and research funding,” she said.

Source: SciTech Daily

Categories : Allergies COVIDTags :

Montelukast Can Block Harmful SARS-CoV-2 Protein and Protect Immune Cells

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Targeting Nsp1 with montelukast helps prevent shutdown of host protein synthesis Credit: Mohammad Afsar

Montelukast can bind to and block a crucial protein produced by SARS-CoV-2, reducing viral replication in human immune cells, according to a new study by researchers at the Indian Institute of Science (IISc).

Montelukast has been around for more than 20 years and is usually prescribed to reduce inflammation caused by conditions like asthma, hay fever and hives.

In the study, published in eLife, the researchers showed that the drug binds strongly to the C-terminal, which is one end of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. NSp1 can bind to ribosomes inside immune cells, shutting down production of vital proteins that the immune system needs, thereby weakening it. Nsp1 could therefore be a target to reduce the virus’s damage.

“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explained IISc’s Assistant Professor Tanweer Hussain, senior author of the study. Since Nsp1 is unlikely to change in future variants, targeting it with drugs is a viable strategy, he added.

The researchers screened more than 1600 FDA-approved drugs with computational modelling to find the ones that bound strongly to Nsp1, coming up with a shortlist of drugs including montelukast and saquinavir, an anti-HIV drug. “The molecular dynamic simulations generate a lot of data, in the range of terabytes, and help to figure out the stability of the drug-bound protein molecule. To analyse these and identify which drugs may work inside the cell was a challenge,” said Mohammad Afsar, first author of the study.

The researchers then cultured human cells which produced Nsp1, treated them with montelukast and saquinavir separately, and found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.

“There are two aspects [to consider]: one is affinity and the other is stability,” explained Afsar. This means that the drug needs to not only bind to the viral protein strongly, but also stay bound for a sufficiently long time to prevent the protein from affecting the host cell, he adds. “The anti-HIV drug (saquinavir) showed good affinity, but not good stability.” Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis.

The researchers then tested the effect of the drug on live viruses and found that the drug was able to reduce viral numbers in infected cells in the culture.

“Clinicians have tried using the drug … and there are reports that said that montelukast reduced hospitalisation in COVID patients,” said A/Prof Hussain, adding that the exact mechanisms behind it still need to be fully understood. His team plans to work with chemists to see if they can modify the structure of the drug to increase its potency, and also plan to continue the hunt for more drugs.

Source: Indian Institute of Science

Categories : Allergies Cardiovascular DiseaseTags :

Allergies Linked to Increased Cardiovascular Risk

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Runny nose and sneezing symptoms
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A national US health survey has revealed that adults with allergies are at an increased risk of hypertension and coronary heart disease, with the biggest risk increase seen in Black male adults. The study is presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference.

“For patients with allergic disorders, routine evaluation of blood pressure and routine examination for coronary heart disease should be given by clinicians to ensure early treatments are given to those with hypertension or coronary heart disease,” said Yang Guo, PhD, the study’s lead author.

An association between allergic disorders and cardiovascular disease was detected in prior research, findings which remained controversial, Dr Guo explained. The present study sought to determine whether an increased cardiovascular risk exists in adults with allergic disorders.

The study used 2012 data from the National Health Interview Survey (NHIS), a cross-sectional survey of the US population. In the allergic group were adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. The study included a total of 34 417 adults, over half of whom were women, average age 48.5 years. The allergic group included 10 045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors.

Having a history of allergic disorders was found to be associated with increased risk of developing hypertension and coronary heart disease. Further analysis showed that individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of hypertension. An increased risk of coronary heart disease was seen in male Black/African American participants between ages 39-57. Asthma was the largest contributor of risk of hypertension and coronary heart disease.

Dr Guo said that to confirmed these findings, large cohort studies with long-term follow-up are required. Discovering the underlying mechanism could also help with management.

Source: American College of Cardiology

Categories : AllergiesTags :

Avoid Goat’s Milk Skin Products in Inflammatory Skin Conditions

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Individuals with inflammatory skin conditions should avoid using skincare products that contain food products such as goat’s milk, according to a series of case studies published in Clinical & Experimental Allergy. Such skincare products have been marketed to those with ‘sensitive skin’.

In children, milk allergy is one of the most common food allergies, but usually resolves in the first years of life. Adult-onset milk allergy is rare. In patients with inflammatory conditions of the skin such as atopic dermatitis, associations between the use of food allergen-containing skin products and systemic sensitisation to that foodstuff has been demonstrated for several foods. This is of concern, as food-containing skin products are commonly promoted as a safer and more ‘natural’ way of managing a variety of skin conditions. These are widely available for unprescribed purchase in pharmacies and supermarkets.

The present study reports on seven patients with inflammatory skin conditions who experienced anaphylaxis after ingesting goat’s or sheep’s milk or cheese products.  All of the patients had a history of using goat’s milk skin products to treat their skin conditions prior to the onset of their allergic reaction. Six of them had atopic dermatitis.

“Marketing of skin products derived from goat’s milk is extensive and targeted to patients with ‘sensitive skin’ who commonly have underlying inflammatory skin conditions,” the authors wrote. “Our findings provide novel evidence of the origins of adult-onset milk allergy and adds to the growing body of evidence that use of foodstuffs as therapy for inflammatory skin conditions can lead to the development of new food allergies.” 

Source: Wiley

Categories : Allergies PaediatricsTags :

Is Milk Allergy Being Overdiagnosed in Infants?

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Current guidelines could be causing cow’s milk allergy to be over-diagnosed in infants, according to a new study. 

Researchers analysed data on 1303 healthy infants who were exclusively breastfed until at least three months of age, and found that 38% and 74% of infants had multiple mild-to-moderate milk allergy symptoms – as defined by current allergy guidelines – at three months and 12 months old, respectively. By comparison, non-IgE-mediated cow’s milk allergy has a prevalence of less than 1% in children.

The researchers’ findings, which are published in Clinical & Experimental Allergy, suggest that following current guidelines may lead to over-diagnoses in infants by labelling normal infant symptoms as possible milk allergies.

“There is an assumption that the existence of a guideline is more beneficial than no guideline. However, well-meaning guidelines need to be supported by robust data to avoid harms from over-diagnosis that exceed the damage of missed and delayed cow’s milk allergy diagnoses that they are seeking to prevent,” the researchers wrote.

Source: Wiley

Categories : Allergies Mental HealthTags :

A Link Between Mental Health and Allergies

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Researchers have reported finding a link between allergic diseases and mental health conditions, but one which was likely not causal.

The analysis of data from the UK Biobank was published in Clinical and Experimental Allergy. The researchers used a genetic instrument derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. They also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever.

The researchers found that people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism. However neither category appeared to play a role in causing the other. Nevertheless, future studies should investigate whether interventions that aim to improve allergic diseases might also have an effect on mental health (and vice versa).

“Our research does not rule out a potential causal effect upon the progression of disease, which is yet to be investigated and could help uncover novel treatment strategies for allergic disease or mental health traits,” said lead author Ashley Budu-Aggrey, PhD, of the University of Bristol.

Senior author Hannah Sallis, MSc, PhD, added that the research used a combination of approaches and data from several studies. “This helps to strengthen our confidence in the findings,” she said. “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Source: Wiley

Categories : Allergies PaediatricsTags :

A Third of Children with Food Allergies are Bullied

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Using a multi-question assessment, researchers found that 1 in 3 children with food allergies reported food allergy-related bullying, indicating the problem is more widespread than commonly believed.

For the study, reported in the Journal of Pediatric Psychology, children were asked a simple ‘yes’ or ‘no’ question about food allergy-related bullying, to which 17% of kids indicated they’d been bullied, teased or harassed about their food allergy. But when asked to reply to a multi-item list of victimisation behaviours, that number jumped to 31%. Furthermore, Children’s National Hospital researchers found that only 12% of parents reported being aware of it. 

The reported bullying ranged from verbal teasing or criticism to more overt acts such as an allergen being waved in their face or intentionally put in their food. Researchers say identifying accurate assessment methods for this problem are critical so children can get the help they need.

“Food allergy-related bullying can have a negative impact on a child’s quality of life. By using a more comprehensive assessment, we found that children with food allergies were bullied more than originally reported and parents may be in the dark about it,” says Linda Herbert, Ph.D., director of the Psychosocial Clinical and Research Program in the Division of Allergy and Immunology at Children’s National and one of the study’s researcher.

“The results of this study demonstrate a need for greater food allergy education and awareness of food allergy-related bullying among communities and schools where food allergy-related bullying is most likely to occur,” Dr Herbert added.

The study examined food allergy-related bullying and evaluated parent-child disagreement and bullying assessment methods. It included 121 children and 121 primary caregivers who completed questionnaires. The children ranged in age from 9 to 15 years of age and had an allergy diagnosis of one or more of the top eight IgE-mediated food allergies: peanut, tree nut, cow’s milk, egg, wheat, soy, shellfish and fish.

Of the 41 youth who reported food allergy-related bullying:

  • 51% reported experiencing overt physical acts such as an allergen being waved in their face, thrown at them or intentionally put in their food.
  • 66% reported bullying experiences including non-physical overt victimisation acts including verbal teasing, remarks or criticisms about their allergy and verbal threats or intimidation.
  • Eight reported relational bullying, such as rumour spreading, people speaking behind their back and being intentionally ignored or excluded due to their food allergy.

The researchers also note that food allergy bullying perpetrators included, but were not limited to, classmates and other students, and bullying most commonly occurred at school.

The authors found that only 12% of parents reported that their child had been bullied because of their food allergy and of those, 93% said their child had reported the bullying to them. Some parents even reported being made fun of or teased themselves because of concerns about their child’s food allergy.

“It’s important to find ways for children to open up about food allergy-related bullying,” Dr Herbert said. “Asking additional specific questions about peer experiences during clinic appointments will hopefully get children and caregivers the help and support they need.

Source: Children’s National Hospital

Categories : AllergiesTags :

New Allergen Pathway Discovery Could Yield New Meds

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Researchers have uncovered the mechanism by which the innate immune system is triggered by allergens, such as insects, mites, and fungi.

In Nature Immunology, researchers revealed new details about how the body’s “type 2 innate immune response” system works, which could yield a new medication for allergy control.

“Disrupting this allergen sensing pathway could provide a unique opportunity to counteract type 2 immunity and alleviate allergic inflammation,” said senior author Marc Rothenberg, MD, PhD, Director, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center

In addition to Rothenberg, the research team included , Mark Rochman, PhD, Yrina Rochman, PhD, Julie Caldwell, PhD. Lydia Mack, MS, Jennifer Felton, PhD, Jeff Habel, PhD, Aleksey Porollo, PhD and Chandrashekhar Pasare, DVM, PhD.

Multiple allergens had been shown to induce a similar IL-33 response upon breaching the epithelial layer of mucosal membranes, a process which the researchers pinned down.

“This breakthrough was made possible by new insights into the role of ripoptosome signaling and caspases in allergic inflammation,” said Michael Brusilovsky, MMedSc, PhD, who was the first author of the study.

Specifically, the allergens trigger activity among an interlocked set of cell death-inducing signals called the ripoptosome. This signaling “platform” includes numerous components, but for allergic inflammatory reactions, the key player appears to be a molecular switch called caspase 8. The investigators named the pathway, “RipIL-33” as IL-33 is processed (ripped) by the ripoptosome.

How allergens are sensed has remained a mystery.

“The discovery of this surprising mechanism is the most important breakthrough in understanding how the innate immune system senses allergens to initiate a type 2 response and subsequent allergic inflammation,” said Pasare, one of the senior authors of the study.

In mice, inhibiting caspase 8 reduced the IL-33 response to allergens and limited bronchial inflammation in the lungs. Analysis revealed a similar process in humans/ 
“In the human allergic disease eosinophilic esophagitis (EoE), we found that ripoptosome activation markers and mature IL-33 levels dynamically correlated with the degree of esophageal eosinophilia and disease activity,” the study states.

The next steps include studying the RipIL-33 pathway in human allergic reaction and determining whether existing or new drugs could disrupt it.

Source: News-Medical.Net

Categories : AllergiesTags :

Allergies in Childhood Linked to Developing Tree Nut Allergies

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A Swedish study found that while allergic sensitivity to tree nuts was common in adults, most people never experienced symptoms.

Allergies to tree nuts are common and have become an important health concern as availability has increased. Tree nuts include hazelnuts, walnuts, pecans, cashews, pistachios, almonds, and brazil nuts.Tree nuts, as a group, are one of the eight most common allergens, and allergic reactions to them can be severe. Availability of tree nuts has increased both in the raw form and within processed foods and bakery products; tree nut utilisation has increased by 1kg per capita from 1980 to 2015. Research has shown that the consumption of nuts has positive cardiovascular effects, such as decreasing cholesterol, triglycerides, and fasting blood glucose, and this has encouraged consumption.

The study, with a total of 2215 participants, found that eczema, asthma, and egg allergies at an early age were associated with developing a tree nut allergy by adulthood. Additionally, the researchers found allergen molecules to be better diagnostic tools for predicting allergic symptoms to tree nuts compared with analysing allergen extracts. The study was published in Clinical and Experimental Allergy.

“This study increases the understanding of tree nut allergy in a general population, followed from infancy up to adulthood. For example, our study reveals that most extract‐based tree nut‐sensitised individuals do not have tree nut allergy and hence extract-based testing for tree nuts without a specific clinical suspicion should not be performed,” said co–lead author Jessica Bager, of the Karolinska Institute.

Source: Wiley