Tag: peanut allergy

Eliminating the Risk of Anaphylaxis from Children’s Peanut Allergy Desensitisation

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Oral immunotherapy helps many children with peanut allergy – but for some, it can also trigger severe allergic reactions. In the journal Allergy, a team led by Young-Ae Lee explains what might be behind these differences and how treatment could become more personalised.

Peanut allergy is one of the most common – and most dangerous – food allergies. Tiny amounts of the protein-rich legumes can be enough to cause allergic reactions like itching and swelling, or even life-threatening anaphylaxis. For a long time, the only solution was to avoid peanuts as vigilantly as possible. Since many foods may contain traces of peanuts, that’s still a major challenge, especially for parents of affected children. Emergency medication must always be close at hand.

Recently, oral desensitisation has become available for children with peanut allergies. “Some children respond well to this treatment, but others don’t benefit at all,” says Professor Young-Ae Lee, Group Leader of the Molecular Genetics of Allergic Diseases lab at the Max Delbrück Center. “In some cases, the therapy – based on gradually increasing doses of peanut allergens – can even trigger anaphylactic reactions.”

A team led by Lee and Professor Kirsten Beyer, Head of the Pediatric Allergy Clinical Research Center at Charité – Universitätsmedizin Berlin, has now investigated why children respond so differently to the therapy and how to make it safer and more effective. Their study, published in “Allergy,” was led by first author Dr Aleix Arnau-Soler, a scientist in Lee’s lab. “We looked for molecular changes in the immune systems of children undergoing oral immunotherapy ¬– and we found them,” explains Arnau-Soler.

Gut immune cells play a key role

For their study, the researchers analyzed blood samples from 38 children, with an average age of seven, who were undergoing oral desensitization for peanut allergy at Charité. The team measured levels of immunoglobulins, which are allergy-related antibodies, and cytokines, which are inflammatory messengers, before and after therapy. 

Our results open the door to personalised approaches to treating peanut allergy – which affects three per cent of all children in industrialised countries – more effectively and safely in the future.

Young-Ae LeeHead of the “Molecular Genetics of Chronic Inflammation and Allergic Disease” lab

They also assessed how much peanut protein each child could tolerate before and after treatment – essentially, how successful the desensitization was. To delve deeper, they used modern omics technologies to identify which genes in the children’s immune cells were activated when they were exposed to peanut proteins in the lab.

“Children who responded well to the therapy already had a less reactive immune system before treatment began. Their blood showed lower levels of immunoglobulins and cytokines,” explains Arnau-Soler. These findings could help identify in advance which children are most likely to benefit from desensitization – and those who are at higher risk of side effects.

The team also found consistent differences in gene expression and DNA methylation patterns between children who responded well and those who didn’t. Methylation plays a key role in regulating gene activity. “These differences were particularly pronounced in certain immune cells that are rarely found in the blood, but more common in the gut, where they perform important functions,” says Arnau-Soler. These included both specialized T cells, part of the adaptive immune system, and cells involved in the body’s innate defenses.

New biomarkers pave the way for personalized therapy

“Our results open the door to personalized approaches to treating peanut allergy – which affects three percent of all children in industrialized countries – more effectively and safely in the future,” says Lee. “We now have potential biomarkers to find out how well a child will respond to the therapy and what risks are associated with it in each individual case, even before the therapy begins.” It may soon be possible to tailor the length of treatment and the amount of peanut allergen given to each child’s unique immune profile.

The team is currently working to validate their findings in a follow-up study. They also plan to further investigate the gut-associated immune cells found in blood. “At the same time, we’re developing a predictive model so that in the future we can use a simple blood test to better tailor oral desensitization to the individual child,” adds Arnau-Soler. That could make peanut allergy far less frightening for families.

Source: Max Delbrück Center for Molecular Medicine

New Guidance Available for Peanut Desensitisation Therapy

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Based on focus groups with children and young people with peanut allergy, experts have published guidance for clinicians working in the UK’s National Health Service (NHS) to help them safely and equitably implement Palforzia® peanut oral immunotherapy. Their recommendations are published in Clinical & Experimental Allergy.

In 2022, the National Institute for Health and Care Excellence in the UK recommended the use of Palforzia® – which has defatted peanut powder as its active ingredient – for desensitising children and young people with peanut allergy in the NHS.

The new consensus guidance will inform and support healthcare professionals as they implement Palforzia® for desensitisation and as they gradually increase peanut dosing in patients.

“It is great we can now offer an actual treatment for peanut allergy, rather than just recommend avoidance and educate patients on how to recognise and manage reactions, but the challenge in our current NHS is how we can provide this to eligible patients equitably, regardless of where they live and their backgrounds,” said corresponding author Tom Marrs, PhD, of Guy’s and St Thomas’ NHS Foundation Trust. “This guidance outlines what NHS services need to be able to offer this treatment at scale and to advocate for patients so that we can develop best-practice models.”

Source: Wiley

Sublingual Immunotherapy for Peanut-Allergic Toddlers is Safer and More Effective

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A three-year clinical trial has shown that the sublingual immunotherapy (SLIT) is safe in peanut-allergic children ages one to four, with a greater likelihood of desensitisation and remission the earlier the treatment began. SLIT approach where the treatment is given as a small amount of liquid under the tongue, instead of peanut flour that is mixed with other food and then eaten like it is during oral immunotherapy, or OIT.

Published in the Journal of Allergy and Clinical Immunology, this is the first randomised, controlled trial to investigate – in this young age group – the efficacy and feasibility of SLIT.

The study included 50 peanut-allergic children between the ages of one and four, randomised to receive 4mg peanut SLIT versus placebo. Participants were randomised 1:1 to receive either peanut SLIT or placebo. Desensitization to peanut was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after three years of treatment.

Findings showed that peanut SLIT can be highly effective in treating peanut-allergic toddlers with almost 80% tolerating 15 peanuts without allergic symptoms after completing the treatment. With most typical peanut-allergic reactions being caused by one peanut or less, these results would translate into strong protection against exposures to peanut. In addition, researchers showed that remission of the peanut allergy may be possible after peanut SLIT with 63% of the toddlers maintaining their protection three months after stopping the treatment. These new findings show that early intervention with peanut SLIT is promising and warrants further development.

Led by Edwin Kim, MD, associate professor of paediatrics at the UNC School of Medicine, said: “From our prior studies in older children, we were optimistic that peanut SLIT could have a similar treatment effect in toddlers.

“However, what we found was even better. The desensitisation levels we saw were higher than expected and on par with levels we normally would only expect with oral immunotherapy. Just as important, rather than wearing off quickly, we were excited to see that over 60% stayed protected three months after stopping the treatment.”

One of the presumed strengths of the SLIT approach when compared to OIT has been its overall safety and simple administration. While most treatment side effects with OIT are mild to moderate, severe reactions requiring emergency treatment do occur and there remains a critical need to develop treatments with more manageable side effects.

“Peanut OIT is currently available and being offered by increasing numbers of allergists, however we are quickly learning that in addition to its known risk of allergic reactions, the actual doing of OIT can be very difficult for many families,” said Kim. “Peanut SLIT could be a good option to consider as it may be able to provide comparable levels of protection while being safe and easier to administer.”

Compared to OIT, the SLIT approach is likely to be a safer option, Kim said, with the most common side effect consisting of oral itching. Treatments that can protect children from allergic reactions while still being safe and practical for busy families can be life-changing, and researchers are hopeful that peanut SLIT can be one of those options.

“Even with the push to introduce peanut in early childhood in order to prevent the allergy, peanut allergy remains one of the most common food allergies,” said Kim. “A result of early peanut introduction is that we are diagnosing peanut allergy at younger and younger ages making it vitally important to develop treatments that can be safe and effective at preventing allergic reactions in these young children.”

Source: UNC School of Medicine

A Regimen of Boiled Peanuts Desensitises Allergy Sufferers

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

The Process of Remission from Peanut Allergy Mapped Out

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