Toddlers allergic to peanuts: Study shows how sublingual immunotherapy is safe and effective

 A three-year clinical trial funded by the National Institutes of Health and Food Allergy Research and Education (FARE) has shown that the sublingual immunotherapy, or SLIT, is safe in peanut-allergic children ages 1 to 4, with a greater likelihood of desensitization and remission the earlier the treatment began.

Led by Edwin Kim, MD, associate professor of pediatrics at the UNC School of Medicine, this is the first randomized, controlled trial to investigate -- in this young age group -- the efficacy and feasibility of SLIT, which involves a tiny bit of peanut protein absorbed under the tongue.

The study, published in the Journal of Allergy and Clinical Immunology, included peanut-allergic 1 to 4 year-old children randomized to receive 4 mg peanut SLIT versus placebo. A total of 50 participants (40 at UNC Medical Center, 10 at University of Texas Southwestern Medical Center) were enrolled. Participants were randomized 1:1 with 25 receiving peanut SLIT and 25 receiving placebo. It's an 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. 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.

"From our prior studies in older children, we were optimistic that peanut SLIT could have a similar treatment effect in toddlers," said Kim, corresponding author of the study, pediatric allergy and immunology division chief and director of the UNC Food Allergy Initiative. "However, what we found was even better. The desensitization 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:ScienceDaily

Black sheep' of helper T cells may hold key to precision allergy treatment

 A new Nature Immunologystudy led by University of Pittsburgh and National Institutes of Health 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, M.D., 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 signaling pathway. The main "on" switch for T cells is when the T cell receptor recognizes 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, Schwartz and her team measured IL9, a cytokine produced by Th9 cells, in T cells from patients with atopic dermatitis, an allergic condition characterized by a dry, itchy rash, 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 hypothesized 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.

sources-science daily

Clinical trial to help millions with penicillin allergie

 Penicillin allergy affects more than 25 million people in the United States (up to 1 in 10 Americans) and has been shown to lead to particularly poor health outcomes in pregnant women and surgical patients. It is also a public health threat, leading to antibiotic resistance and infections in hospitalized patients that can be life threatening.

Seventy-five% or more 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 multicenter randomized control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) study.

In the PALACE study, investigators randomized 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 labeled 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, the John Oates Professor of Clinical Research. "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 specialized centers 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.

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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 diarrhea due to Clostridioides difficile, which can spread through hospitals and become a major public health problem." Phillips said. "In the U.S. 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 specialized 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.

The PALACE study was led by Ana-Maria Copaescu, MD, PhD, McGill University Health Centre, Montréal, and senior author Jason Trubiano. PhD, Center for Antibiotic Allergy and Research, Department of Infectious Diseases at Austin Health. Cosby Stone, MD, assistant professor of Medicine in the Division of Allergy, Pulmonology, and Critical Care Medicine, was a co-investigator for VUMC.

sources-science daily

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Food allergy in infancy linked to childhood asthma and reduced lung function

 Having a food allergy as a baby is linked to asthma and reduced lung function later in childhood, according to a world first study.

The research, led by Murdoch Children's Research Institute and published in the Lancet Child & Adolescent Health, 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, including peanut and egg and oral food challenges to test for food allergy. 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 per cent 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.

sources-science daily

Allergy study on 'wild' mice challenges the hygiene hypothesis

 The notion that some level of microbial exposure might reduce our risk of developing allergies has arisen over the last few decades and has been termed the hygiene hypothesis. Now, an article published in Science Immunology by researchers from Karolinska Institutet challenges this hypothesis by showing that mice with high infectious exposures from birth have the same, if not an even greater ability to develop allergic immune responses than 'clean' laboratory mice.

How microbes may prevent allergy has been a topic of great interest in recent times. Studies have suggested that certain infections might reduce the production of inflammatory antibodies to allergens and alter the behaviour of T cells involved in allergies. It has also been suggested that good bacteria in our intestines may be able to switch off inflammation in other parts of our body.

Robust allergic responses

Researchers have now compared the allergic immune response in 'dirty' wildling mice to those of typical clean laboratory mice. They found very little evidence that the antibody response was altered or that the function of T cells changed in a meaningful way. Nor did anti-inflammatory responses evoked by good gut bacteria appear to be capable of switching off the allergic immune response. On the contrary, wildling mice developed robust signs of pathological inflammation and allergic responses when exposed to allergens.

"This was a little unexpected but suggests that it's not as simple as saying, 'dirty lifestyles will stop allergies while clean lifestyles may set them off'. There are probably very specific contexts where this is true, but it is perhaps not a general rule," says Jonathan Coquet, co-author of the study and Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet in Sweden.

More like the human immune system

The wildling mice are genetically identical to clean laboratory mice but are housed under seminatural conditions and have rich microbial exposures from birth.

sources-science daily

Toddlers allergic to peanuts: Study shows how sublingual immunotherapy is safe and effective

 A three-year clinical trial funded by the National Institutes of Health and Food Allergy Research and Education (FARE) has shown that the sublingual immunotherapy, or SLIT, is safe in peanut-allergic children ages 1 to 4, with a greater likelihood of desensitization and remission the earlier the treatment began.

Led by Edwin Kim, MD, associate professor of pediatrics at the UNC School of Medicine, this is the first randomized, controlled trial to investigate -- in this young age group -- the efficacy and feasibility of SLIT, which involves a tiny bit of peanut protein absorbed under the tongue.

The study, published in the Journal of Allergy and Clinical Immunology, included peanut-allergic 1 to 4 year-old children randomized to receive 4 mg peanut SLIT versus placebo. A total of 50 participants (40 at UNC Medical Center, 10 at University of Texas Southwestern Medical Center) were enrolled. Participants were randomized 1:1 with 25 receiving peanut SLIT and 25 receiving placebo. It's an 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. 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.

"From our prior studies in older children, we were optimistic that peanut SLIT could have a similar treatment effect in toddlers," said Kim, corresponding author of the study, pediatric allergy and immunology division chief and director of the UNC Food Allergy Initiative. "However, what we found was even better. The desensitization 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."

sources-science daily

Could the nerve cells that scratch be the solution for itch?

 It can be a relief to scratch the occasional itch, but when itch gets out of control, it can become a serious health problem. How does the body know when to stop?

Scientists at UC San Francisco are getting close to an answer. In a breakthrough that could transform how doctors treat conditions from eczema to allergies, they have discovered a feedback loop centered on a single immune protein called IL-31 that both causes the urge to itch and dials back nearby inflammation.

The findings, published on October 13th in Science Immunology, lay the groundwork for a new generation of drugs that interact more intelligently with the body's innate ability to self-regulate.

Previous approaches suggested that IL-31 signals itch and promotes skin inflammation. But the UCSF team discovered that nerve cells, or neurons, that respond to IL-31, triggering a scratch, also prevent immune cells from overreacting and causing more widespread irritation.

"We tend to think that immune proteins like IL-31 help immune cells talk to one another, but here, when IL-31 talks to neurons, the neurons talk right back," said Marlys Fassett, M.D., Ph.D., UCSF professor of dermatology and lead author of the study. "It's the first time we've seen the nervous system directly tamp down an allergic response."

The discovery could eventually change how asthma, Crohn's and other inflammatory diseases are treated, due to IL-31's presence throughout the body.

"IL-31 causes itch in the skin, but it's also in the lung and in the gut," said Mark Ansel, Ph.D., UCSF professor of immunology and senior author of the study. "We now have a new lead for fighting the many diseases involving both the immune and nervous systems."

More than an itch

sources-science daily