Category: Allergies

Categories : AllergiesTags :

Researchers Identify the Bacteria Behind the Protective “Farm Effect”

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An international research team led by Prof. Markus Ege of LMU University Hospital has, for the first time, identified which bacteria in barn air are responsible for the so-called “farm effect,” which can protect against allergies, asthma, and hay fever. Photo by Christopher Stites on Unsplash

An international research team has identified for the first time which bacteria in barn air are responsible for the ‘farm effect’ that can protect against allergies, asthma, and hay fever.

Children who grow up in a farm environment are less prone to allergies, asthma, and hay fever than  their classmates. This so-called farm effect has been identified in several observational studies worldwide. It is most likely attributable to the fact that various bacteria present in barn air prevent excessive inflammatory responses of the immune system that are characteristic of such diseases. But which bacteria exactly?

Now, an international team led by Professor Markus Ege from the Dr. von Hauner Children’s Hospital at LMU University Hospital and the Institute of Asthma and Allergy Prevention at Helmholtz Munich has answered this question. The researchers have shown for the first time which specific bacteria in barn air trigger the farm effect, which substances within those bacteria mediate the protection, and which receptors in the body they bind to. Their findings have been published in The New England Journal of Medicine – Evidence.

For years we have been hearing about the hygiene hypothesis, which was first proposed in 1989. This came after three decades of dramatic increases in allergies, asthma, and hay fever among children in Western industrialised countries. These are all conditions in which the immune system mounts an exaggerated inflammatory response and mistakenly attacks the body’s own tissues. According to the hygiene hypothesis, this happens because of under-stimulation in early childhood. The immune systems of children who encounter too few environmental microbes and common cold viruses are more likely to malfunction. “Girls and boys who grow up on farms and are exposed to a wider variety of microbes have the problem far less often,” says Ege. As their immune systems constantly contend with bacterial ‘sparring partners’ from barn air, they are trained to avoid excessive inflammatory responses.

However, the hygiene hypothesis has not been definitively proven, as it is largely based on observational studies. “This kind of research can only show more or less convincing correlations,” says epidemiologist Ege. “But with our new study, we can make a much stronger case, because we can identify the individual links in the proposed causal chain: the bacteria, the relevant microbial metabolic products, and the human receptors.”

The Approach

The researchers analysed data from more than 1000 children participating in European studies in rural areas. For all the children, girls and boys, two types of samples had been collected: nasal swabs and mattress dust. In addition, dust samples were taken from cowsheds for 47 farm children. The team examined which bacteria and fungi were present in these samples, how the different microorganisms were related, and whether specific microbial groups protected the children against asthma.

To this end, the epidemiologists and bioinformaticians employed state-of-the-art genetic and metabolic analyses and developed computer models. Through a process of elimination, they eventually identified the key microorganisms. They also investigated whether the children’s own genes influenced this protective effect. To validate their findings, the researchers additionally used data from France and Finland.

The Results

We identified a small number of bacteria, which we can now pinpoint down to the species level,” explains Giulia Pagani, first author of the study and bioinformatician at the Institute of Asthma and Allergy Prevention at Helmholtz Munich, “such as Romboutsia timonensis and Glutamicibacter arilaitensis. These gram-positive bacteria together mediate two-thirds of the entire farm effect for asthma protection and half of the effect for hay fever and atopic eczema.” The bacteria originate in the cow’s digestive tract, where they produce or metabolize substances like kynurenine, xanthine, alpha-linolenic acid, and stearidonic acid. These compounds are easily inhaled and recognized by two receptors on human airway cells – AhR and PPARγ. “These receptors,” Ege continues, “have multiple functions, including in the immune system, where they appear to prevent excessive inflammatory responses.” Their role in the farm effect was previously unknown. For the first time, therefore, the complete biological chain is visible: cow → barn air → bacteria → metabolic products → human receptors → protection against asthma.

The new findings can now be used by laboratory researchers to decipher the molecular and cellular mechanisms of the farm effect. This opens up the prospect of developing a drug that mimics the farm effect – without the need for children to spend time in barns.

Original publication

G. Pagani et al.: Gram-Positive Bacteria and the Inverse Association between Farm Exposure and Childhood Asthma, NEJM Evidence

DOI: https://doi.org/10.1056/EVIDoa2500271

Source: LMU Klinikum München

Categories : Allergies Respiratory DiseasesTags :

Researchers Reveal Iron’s Role in Allergic Airway Inflammation

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Respiratory tract. Credit: Scientific Animations CC4.0

Chinese researchers have revealed the key role of iron in initiating allergic airway inflammation. The study, which was published in Cell, was conducted by a team led by Prof SUN Bing from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences (CAS), along with Prof LIU Xing’s team from the Shanghai Institute of Materia and Medica of CAS.

The research showed that environmental allergens can use an iron-dependent mechanism to activate gasdermin D (GSDMD) in airway epithelial cells, thereby promoting IL-33 release and initiating allergic airway inflammation – the main pathological basis for the onset and progression of asthma.

When environmental allergens such as pollen, house dust mites, and fungal proteases enter the airway, they act on lung epithelial cells and induce the release of alarmins, including IL-33. IL-33 then activates type 2 innate lymphoid cells (ILC2s), leading to eosinophil infiltration, mucus production, and airway tissue damage.

Previous studies have shown that GSDMD is involved in IL-33 release, but how allergens activate GSDMD had remained unclear. In this study, the researchers found that allergen stimulation rapidly increased the labile iron pool in airway epithelial cells, and GSDMD was cleaved and activated through a mechanism independent of conventional proteases.

Using mouse models induced by papain or house dust mites, the researchers observed a rapid rise in lung iron levels after allergen challenge, occurring in parallel with IL-33 release. Treatment with an iron chelator markedly inhibited GSDMD cleavage and IL-33 release, whereas iron supplementation enhanced these responses. This iron-driven effect was largely abolished in GSDMD-deficient mice, indicating that the pro-inflammatory activity of iron is highly dependent on GSDMD.

Furthermore, the researchers showed that cell-surface protease-activated receptor PAR1 serves as an important entry point for allergen sensing. Papain directly cleaves PAR1, which in turn initiates NCOA4-mediated ferritinophagy and releases additional free iron. The iron chaperone PCBP2 delivers iron to the vicinity of GSDMD, where the E309/Q312 residues of GSDMD are responsible for iron binding. When these sites are mutated, GSDMD can no longer be efficiently cleaved or mediate IL-33 release.

The researchers found that this cleavage process does not depend on canonical inflammasome-associated caspases. Instead, iron delivered by PCBP2 locally triggers a Fenton reaction, generating short-range hydroxyl radicals that drive oxidative cleavage of GSDMD.

In vivo experiments showed that pretreatment with the iron chelator DFP significantly alleviates papain-induced airway inflammation, reducing eosinophil infiltration, IL-5 and IL-13 levels, and mucus secretion. Conversely, iron supplementation aggravated inflammatory responses in wild-type mice, but failed to produce the same effect in GSDMD-deficient mice.

These findings establish the iron–GSDMD–IL-33 axis as an important driver of allergen-induced type 2 immune responses, and suggest that PAR1, iron mobilisation, PCBP2, and local iron-mediated reactions may represent potential intervention points for asthma and other allergic diseases.

In summary, this study proposes a new mechanism for the initiation of allergic airway inflammation. It expands the understanding of GSDMD activation and immunological functions of iron metabolism, and provides new insight into the prevention and treatment of asthma and related allergic diseases.

Source: Chinese Academy of Sciences

Categories : Allergies Respiratory DiseasesTags :

No Worsening in Children’s Asthma when Living With Cats

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Children with asthma and allergies who live with one or more cats do not experience worse asthma outcomes than children without cats at home. This is according to a comprehensive Swedish registry study from Karolinska Institutet, published in Frontiers in Allergy.

Many families with asthmatic children are advised to avoid keeping furry pets in the home. At the same time, previous studies on how cats as pets affect children with asthma and allergies have often been small and produced conflicting results.

The new study covers over 30 000 children in Sweden aged 4–17 with diagnosed asthma and allergies. The researchers followed the children for two years, comparing those living in households with cats with those who did not. Data on cat ownership was obtained from the national cat register and combined with data from several Swedish health and quality registers.

“We found no evidence that living with cats worsens asthma in children who already have asthma and allergies,” says Resthie R. Putri, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “Unfortunately, however, we had no information on the specific allergies the children had, so we do not know whether they were allergic to cats or not.” 

Individual advice is needed

The researchers analysed asthma exacerbations leading to emergency care, asthma severity based on medication use, asthma control, and lung function in the children. Children living with one or more cats experienced similar asthma outcomes to those without a cat. Nor could the number of cats in the home, or the age or sex of the cat, be linked to differences in asthma outcomes.

One strength of the study is the large number of participants from across Sweden. However, differences between countries may limit the applicability of the results to other contexts. As the Cat Register is relatively new, some cat exposure may not have been captured in the study. Furthermore, there was no information on how long the children had been exposed to cats for, or how much time the cats spent indoors. The researchers also cannot rule out the possibility that families with children suffering from more severe allergies may have chosen not to keep a cat.

“Clinical advice always needs to be tailored to the individual, and our study can contribute to the evidence base in discussions with families about pets and asthma,” says Catarina Almqvist Malmros, professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and paediatrician at Astrid Lindgren Children’s Hospital.

Will continue to follow the children

The researchers now plan to continue studying how different types of allergies may affect the outcome, and whether it makes a difference if the child is allergic to cats. They also plan to follow the children for a longer period to see how cat ownership may affect asthma over time.

Source: Karolinska Institutet

Categories : Allergies VaccinesTags :

New mRNA Vaccine Could Prevent Seasonal and Food Allergies

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A new mRNA vaccine stopped allergens from causing dangerous immune reactions and life-threatening inflammation in mice, according to researchers from the Perelman School of Medicine at the University of Pennsylvania and Cincinnati Children’s. The vaccine, outlined in the Journal of Clinical Investigation, may one day be tested and tailored to a variety of seasonal and food allergies.

“This is a potential breakthrough for millions of people worldwide who suffer from life-threatening allergies,” said Nobel laureate Drew Weissman, MD, PhD, Professor in Vaccine Research at Penn and co-lead of the study with Cincinnati Children’s Marc E. Rothenberg, MD, PhD.

Weissman, Penn colleagues Jilian Melamed, PhD, an assistant professor of Infectious Diseases, Mohamad-Gabriel Alameh, PhD, an assistant professor of Pathology and Laboratory Medicine, and the Cincinnati Children’s researchers led by Marc E. Rothenberg, MD, PhD, director of the division of Allergy and Immunology, modelled this new vaccine on the design of the COVID-19 mRNA lipid nanoparticle (LNP) vaccines.

This time, however, scientists tweaked the mRNA to instruct cells to produce proteins that resemble certain allergens. By presenting these proteins in a controlled way, the vaccine didn’t cause allergic reactions but did instruct the immune system to respond more appropriately in the future. And, when mice were later exposed to the respective allergens, the vaccines worked.

When mice with specific allergies were exposed to the allergens, none of the mice vaccinated with the respective allergy vaccine had an allergic reaction. Vaccinated mice had fewer allergy-related white blood cells, made fewer inflammation-causing proteins, and their lungs produced less mucus. Their airways were also protected against narrowing, which often happens during asthma, and they made special antibodies that protected against allergic reactions.

A platform with broad potential

Unlike traditional allergy shots, which involve repeated administration of purified allergens over months or years, the mRNA-based approach offers a more flexible solution. Because the mRNA can be tailored to encode proteins from different allergens, the platform could be adapted to treat a wide range of allergic conditions—from seasonal pollen allergies to food sensitivities and asthma. Additionally, many severe food allergies do not have vaccines to protect against severe allergic reactions.

“People with food allergies that can cause anaphylactic shock are rightfully fearful in social situations, eating out in public, sharing food, and engaging in other fun activities where there are food and allergens around,” said Weissman. “Allowing people to partake in foods they were never able to eat would be incredibly rewarding, but I’ll even be happy if we can one day introduce a vaccine that allows parents to breathe just a little easier when sending their kids to class birthday parties.”

The study represents a proof-of-concept that mRNA vaccines can be used not only to prevent infectious diseases but also to adjust immune responses in chronic conditions like allergies and even celiac disease. Researchers say the next steps include testing the vaccine’s safety in humans, determining how many allergens can be included in a single dose, and evaluating how long protection lasts.

“We saw mRNA vaccines save lives during the pandemic, and as the most-tested type of vaccine in history, we know it’s the safest and most effective vaccine ever created,” said Weissman. “We are deeply committed to continuing to uncover the potential of this technology.”

Source: Perelman School of Medicine at the University of Pennsylvania

Categories : Allergies Mental HealthTags :

Allergy Season Linked to an Increase in Suicide Risk

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Beyond the sneezing and itchy eyes, high pollen seasons are now linked to a significant increase in suicide risk. A new University of Michigan study found a 7.4% jump in deaths, suggesting the physical discomfort of allergies may trigger a deeper, more dangerous despair, an overlooked factor in suicide prevention.

The study indicates that allergies’ physiological effects, such as poor sleep and mental distress, may contribute to this increased risk.

“A small shock could have a big effect if you’re already in a vulnerable state,” said Joelle Abramowitz, associate research scientist at U-M’s Institute for Social Research. “We looked specifically at pollen from all different kinds of plants, including trees, weeds and grasses.”

The effect is incremental. Researchers divided pollen levels into four tiers and found the suicide risk rose with each group: it increased by 4.5% in the second level, 5.5% in the third and peaked at 7.4% in the fourth and highest category.

The study, funded by the American Foundation for Suicide Prevention and U-M ISR, combines daily pollen data from 186 counties of 34 metropolitan areas across the United States, with suicide data from the National Violent Death Reporting System between 2006 and 2018.

Abramowitz and co-authors Shooshan Danagoulian and Owen Fleming of Wayne State University said that while structural factors for suicide are well-researched, short-term triggers are less understood. Pollen allergies are an ideal subject for this research, considering they are an exogenous shock – meaning they are external and not caused by an individual’s mental health status.

“During our study period, there were nearly 500 000 suicides in the US,” Abramowitz said. “Based on our incremental data, we estimate that pollen may have been a contributing factor in up to 12 000 of those deaths over the period, or roughly 900 to 1200 deaths per year.”

Vulnerable populations

Published in the Journal of Health Economics, the study also found that individuals with a known mental health condition or who had received prior mental health treatment had an 8.6% higher incidence of suicide on days with the highest pollen levels. White men strongly drive the effect, but the study also found an unexpectedly high vulnerability among Black individuals.

“While our study’s data comes from the U.S., our findings likely apply globally,” Abramowitz said. “This is supported by earlier research that found similar relationships in locations like Tokyo and Denmark. Our results, therefore, provide crucial new evidence that this phenomenon is a consistent, worldwide trend.”

Public health and awareness

The focus should be on public health and education, as reducing the number of pollen-producing plants isn’t a viable option, the researchers suggest. This includes more accurate pollen forecasting and better public communication. Providing people with clear, timely information about high-pollen days allows them to take proactive steps. Additional recommendations are limiting outdoor activities, wearing a mask or having antihistamines on hand.

There is also a need for a broader approach to mental health awareness, the authors said. Health care providers, particularly those in primary care, can benefit from understanding the connection between environmental factors, such as pollen, and patient well-being. This knowledge could help them tailor care more effectively, especially for vulnerable patients, and serve as a prompt to discuss mental health and stress management during high-pollen seasons or other periods of environmental stress.

“We should be more conscious of our responsiveness to small environmental changes, such as pollen, and our mental health in general,” Abramowitz said. “Given our findings, I believe medical providers should be aware of a patient’s allergy history, as other research has also established a connection between allergies and a higher risk for suicide. I hope this research can lead to more tailored care and, ultimately, save lives.”

The authors predict that as climate change extends and intensifies the pollen season, the impact of allergies on suicide rates could more than double by the end of the century.

Source: University of Michigan

Categories : Allergies Lab Tests and ImagingTags :

From Symptoms to Solutions: Professional Testing Can Reveal Hidden Allergens

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As spring arrives in South Africa, many people experience their most challenging allergy season. However, while pollen-filled air triggers obvious seasonal symptoms, allergies extend far beyond springtime discomfort, affecting millions year-round through food sensitivities, skin reactions, and environmental triggers.

“Spring allergies are usually just the tip of the iceberg,” says Tyron Hansen, Business Development Manager at BioSmart Lab. “You wake to spring sunshine and nature in full bloom, but instead of enjoying it, you’re shut inside with tissues and antihistamines. Meanwhile, your stomach acts up after breakfast, and that mysterious rash on your arms is back. Sound familiar?”

Hansen explains that many people assume that their symptoms stem from a single source, like pollen or food preservatives. However, BioSmart Lab’s test results often reveal they’ve actually been living with multiple triggers they never connected to their symptoms.

Why It’s Worth Looking Deeper

Professional allergen tests measure specific antibodies in your blood to identify how your body reacts to different substances. This matters because what looks like “seasonal” hay fever might actually be a mix of environmental, food, and even skin-related triggers.

“Our immune systems are like complicated alarm systems,” explains Hansen. “They go off loudly, but without proper testing, you only hear the siren – you don’t see what’s actually setting it off.”

A major source of confusion is the difference between allergies and intolerances. Both of which can make you feel unwell, but function very differently:

  • Allergies: They set off the immune system through immunoglobulin E (IgE) antibodies, causing anything from a runny nose or itchy eyes to potentially life-threatening anaphylaxis, often within minutes of exposure.
  • Intolerances: These don’t set off your immune system, but they can still cause digestive discomfort like bloating or nausea, and while not dangerous, they can nevertheless affect daily life.

“Knowing which is which can be the key to finally feeling better,” he adds.

Everyday Triggers You Might Be Missing

Allergies aren’t always obvious or seasonal. Many people live with daily discomfort without realising what’s behind it. Hansen provides some of the most common sources of ongoing allergic reactions.

  • Environmental triggers: Dust mites, mould spores, pet dander, and certain plants can cause year-round congestion, itchy eyes, or skin flare-ups.
  • Food sensitivities: That heavy, bloated feeling after meals could point to, for example, wheat, rice and corn sensitivity, or even certain food combinations.
  • Skin reactions: Chronic eczema or rashes are sometimes triggered by hidden allergens, not simply “sensitive skin.”
  • Allergic clues in children: Kids often can’t articulate their symptoms. What might appear to be frequent colds, skin rashes, or trouble concentrating could be subtle signs of allergies.

“Trying to figure out if your symptoms are caused by allergens through elimination diets, behavioural adjustments, or symptom tracking can take months and still leave you without answers, notes Hansen. “Blood-based testing provides a faster alternative by measuring IgE antibodies – the proteins your immune system releases when it detects threats.”

Taking Back Control

BioSmart Lab’s advanced blood panels analyse these IgE proteins across multiple allergens simultaneously. These tests can be purchased online and provide accurate, quantitative results without the risk of sparking reactions or being influenced by medication use.

Some people discover that they need to remove wheat to manage food allergies. Others learn that their “pet allergy” is actually a dust mite sensitivity. Parents often find their child’s mid-afternoon meltdowns are directly linked to specific food triggers at lunch.

“The goal isn’t just to manage symptoms – it’s to restore people’s quality of life,” emphasises Hansen. “Once you understand what your body is reacting to, you can move from frustrating guesswork to making informed choices, giving you control of your health back,” he concludes.

For more information about BioSmart’s allergy testing options, visit https://biosmart.com/allergy-tests/.

Categories : Allergies PaediatricsTags :

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

Categories : AllergiesTags :

Nasal ‘Molecular Shield’ May Soon Treat a Common Pollen Allergy

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Approximately 40% of the European population are allergic to pollen, and their symptoms cause an estimated loss of 100 million school- and workdays every year. The prevalence of hay fever has been surging for decades and this is likely to continue – a change so fast that genetic and health changes can’t be solely responsible. Improved hygiene, the widespread use of antibiotics and antiseptics, lifestyle changes, diet, pollution, and the climate crisis are also thought to play a major role in this increase.

But now there is new hope for sufferers. As proof-of-principle, researchers have engineered an antibody from mice, which when applied to the inside of the nose stops mice from developing hay fever and asthma symptoms in response to mugwort pollen. Mugwort is the most common cause of pollen allergies in central Asia and parts of Europe, where between 10% and 15% of people with hay fever are allergic to it. The article was published in Frontiers in Immunology.

“This is the first time a monoclonal antibody designed to block a specific pollen allergen has been delivered directly into the nose, and been shown to protect against allergy symptoms in the upper and lower airways,” said Prof Kaissar Tabynov, the director of the International Center for Vaccinology at the Kazakh National Agrarian Research University (KazNARU) in Almaty, and the study’s senior author.

“In the future, similar antibodies could be developed for other major pollen allergens, such as ragweed or grass. This opens the door to a new generation of precision allergy treatments that are fast-acting, needle-free, and tailored to individual allergen sensitivities.”

‘Molecular shield’

Traditional treatment is allergen-specific immunotherapy: patients are exposed to gradually increasing doses of the allergen, until they become desensitised. However, this doesn’t work for all patients, and in recent decades, so-called ‘allergen-specific monoclonal antibody therapy’ has increasingly come to the fore as an alternative.

In allergen-specific monoclonal antibody therapy, researchers engineer antibodies of the IgG class, which either specifically recognise the allergen itself and block it, or bind to IgE antibodies in general. In either case, this prevents the allergen from triggering an allergic reaction. A disadvantage is that typically, these antibodies needed to be injected into the bloodstream – until now.

“Our method acts immediately and locally at the lining of the nose, by neutralising the allergen on contact. This ‘molecular shield’ not only prevents IgE antibodies from being activated, but may also reduce inflammation through other mechanisms, such as calming immune cell responses and promoting regulatory pathways,” explained Tabynov.

The researchers injected mice with a dose of mugwort pollen, stimulating them to produce antibodies against it. The mice were then humanely euthanised and their spleens harvested to isolate white blood cells. The use of mice was approved by the local Institutional Animal Care and Use Committee, under the Ministry of Health of the Republic of Kazakhstan.

The white blood cells were then fused with laboratory-grown cancer cells from mice with multiple myeloma. This yielded five immortal ‘hybridoma’ cell lines which each secreted a single type (hence ‘monoclonal’) of antibody against mugwort pollen. A suite of diagnostic tests showed that the most powerful was produced by hybridoma cell line XA19, which was selected for further development.

Reduction in allergy symptoms

To test their efficacy, purified antibodies from XA19 were administered to the interior of the nose of five mice, which had been stimulated to become allergic to mugwort pollen through injections of pollen extract. Five additional mice served as positive control: they had been similarly sensitized but received a placebo. A further five mice were the negative control, neither sensitized to the pollen nor given monoclonal antibodies. Three weeks later, all mice were exposed three times under anaesthesia to an aerosol of mugwort pollen, as well as to pollen extract delivered directly inside the nose.

The results showed that the sensitized mice given the XA19 antibody displayed a major reduction in allergy symptoms compared to controls: for example, they showed a weaker ear swelling response to the pollen (a common allergic reaction in rodents); they rubbed their nose less frequently, indicating less irritation of the upper airways; their full lung capacity was preserved upon exposure to the pollen; and they showed less inflammation inside the nostrils. Inside the lungs, levels of two inflammation-promoting molecules called cytokines were likewise reduced.

The researchers concluded that the monoclonal antibody from XA19 is effective in blocking allergic reactions against mugwort pollen triggered by IgE, at least in mice.

“Before this treatment can be tested in people, we need to adapt the antibody to make it suitable for humans – a process called ‘humanisation’ – and conduct additional preclinical safety and efficacy studies,” said Tabynov.

“If these are successful and provided we have adequate support, we could begin clinical trials in two to three years, though bringing it to market would likely take five to seven years. We are already planning for this transition and working on scaling up production.”

Source: Frontiers

Categories : Allergies Respiratory DiseasesTags :

Inflammatory Cells Remain in the Blood After Treatment of Severe Asthma with Biologics

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Biological drugs have improved the lives of many people with severe asthma. However, a new study from Karolinska Institutet shows that some immune cells with high inflammatory potential are not completely eradicated after treatment.

Biological drugs have become an important tool in the treatment of severe asthma. 

“They help most patients to keep their symptoms under control, but exactly how these drugs affect the immune system has so far remained unknown,” says Valentyna Yasinska, consultant in pulmonary medicine at Karolinska University Hospital and doctoral student at Karolinska Institutet’s Department of Medicine in Huddinge.

Increased in blood

In a new study published in the scientific journal Allergy, researchers at Karolinska Institutet have explored what happens to the immune cells of patients being treated with biologics. By analysing blood samples from 40 patients before and during treatment, they found that instead of disappearing during treatment, certain types of immune cell – which play a key part in asthma inflammation – actually increased.

“This suggests that biologics might not attack the root of the problem, no matter how much they help asthma patients during treatment,” says Jenny Mjösberg, professor of tissue immunology at Karolinska Institutet’s Department of Medicine in Huddinge. “Continued treatment might be necessary to keep the disease under control.”

Surprising finding

The study is based on data from patients with severe asthma sourced from the BIOCROSS study. The researchers used advanced methods such as flow cytometry and single-cell sequencing to determine the properties and function of the immune cells.

“We were surprised to find that blood levels of inflammatory cells increased rather than decreased,” says Lorenz Wirth, doctoral student at the same department at Karolinska Institutet. “This could explain why inflammation of the airways often returns when the treatment is tapered or discontinued. It is important that we understand the long-term immunological effects of these drugs.”

Relatively new drugs

Little is still known about the long-term effects of biologics like mepolizumab and dupilumab since they are relatively new, having been prescribed to asthmatics for less than ten years. 

The next stage of the study will be to analyse samples from patients with a long treatment history and to study lung tissue to see how the immune cells are affected in the airways.

Source: Karolinska Instutet

Categories : Allergies DermatologyTags :

Can Early Exposure to Dogs Lessen Genetic Susceptibility to Eczema?

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New research published in Allergy indicates that certain environmental exposures may affect a child’s risk of developing atopic eczema, a condition characterised by dry, itchy, and inflamed skin. In other words, although some people may be genetically predisposed to eczema, certain environmental factors may increase or decrease that risk.

For the study, investigators analysed data from 16 European studies to test for interactions between the 24 most significant eczema-associated genetic variants and 18 early-life environmental factors. They applied their findings to an additional 10 studies and used lab modelling tests to assess their results.

The first analysis (including 25 339 individuals) showed suggestive evidence for interaction between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking, and washing practices) and at least one established genetic variant for eczema, with 14 interactions in total.

In the additional analysis (254 532 individuals), dog exposure interacted with a particular genetic risk variant on chromosome 5, near the gene that codes for the interleukin-7 receptor, a protein involved in immune cell function. Lab modelling tests showed that this variant affects expression of interleukin-7 receptor in human skin cells and that dog exposure modifies the genetic effect of this variant on the development of eczema, essentially providing a protective effect by suppressing skin inflammation.

Additional studies are needed to explore these lab findings and the other potential interactions identified in the first analysis.

“Our research aims to answer some of the most difficult questions that I am asked in clinic: ‘Why does my child have eczema?’ and ‘What can I do to help protect my baby?’ We know that genetic make-up affects a child’s risk of developing eczema and previous studies have shown that owning a pet dog may be protective, but this is the first study to show how this may occur at a molecular level,” said corresponding author Sara J. Brown, MD, PhD, FRCPE, of the University of Edinburgh. “More work is needed, but our findings mean we have a chance to intervene in the rise of allergic disease, to protect future generations.”

Source: Wiley