Mouse study discovery points to potential new drug targets for treating asthma, hay fever, and other inflammatory disorders

JOHNS HOPKINS UNIVERSITY BLOOMBERG SCHOOL OF PUBLIC HEALTH

Researchers at Johns Hopkins Bloomberg School of Public Health have identified the sequence of molecular events by which tiny, tick-like creatures called house dust mites trigger asthma and allergic rhinitis.

The researchers, whose study was published online June 22 in Nature Immunology, found that allergy-triggering molecules from dust mites can interact with an immune protein called SAA1, which is better known as a sentinel against bacteria and other infectious agents. The researchers showed step-by-step how this interaction between mite-molecules and SAA1 triggers an allergic-type immune response in mice.

The findings reveal what may be a significant new pathway by which allergic and inflammatory disorders arise. They also suggest that blocking the pathway could potentially work as a preventive or treatment strategy against asthma and other allergic reactions.

“We think that the signaling interactions that occur immediately downstream of the mite-proteins’ activation of SAA1 may be good targets for future drugs,” says study senior author Marsha Wills-Karp, PhD, the Anna M. Baetjer Professor of Environmental Health and Chair of the Department of Environmental Health and Engineering at the Bloomberg School.

Asthma affects between 8 to 15 percent of people in the U.S., and is typically triggered by dust mites, tree and grass pollens, and other allergens. Researchers suspect that this inappropriate immune triggering happens when the immune system mistakes allergens–which are otherwise harmless–for pieces of bacteria or other infectious agents. However, the molecular mechanisms underlying this misidentification haven’t been well understood.

In their study, Wills-Karp and her colleagues zeroed in on SAA1, an immune protein that is found, among other places, in the fluid that lines the airways and other mucosal surfaces. A member of the evolutionarily ancient “innate immune system” of mammals, SAA1 is thought to have evolved as a sentinel or early-responder molecule that, for example, recognizes and helps clear away certain types of bacteria and other infectious agents.

The researchers found that exposure to dust-mite proteins causes an asthma-like sensitization of the airways of the control group mice. In contrast, exposure to dust-mite proteins hardly had any effect in mice in which SAA1 was neutralized by antibodies, or in mice whose genes for SAA1 were knocked out. Further experiments confirmed that SAA1, when it is present, directly binds certain dust-mite allergens called fatty-acid binding proteins, which have structural similarities with proteins found in some bacteria and parasites. This allergen-SAA1 interaction releases SAA1 into its active form, wherein it activates a receptor called FPR2 on airway-lining cells. The airway cells then produce and secrete large quantities of interleukin-33, a protein known for its ability to stimulate allergic-type immune responses.

Confirming the likely relevance to humans, the researchers found evidence of increased production of SAA1 and FPR2 in nasal airway-lining cells from patients with chronic sinusitis–which is often linked to dust-mite allergens–compared to healthy controls.

“We think that different allergens take different routes to the activation of interleukin-33 and related allergic responses, and this SAA1-FPR2 route seems to be one that is taken by some dust-mite allergens,” Wills-Karp says.

She and her colleagues now plan to investigate why some people develop allergic disorders in which this pathway is hyperactive, while most don’t. They also plan to explore the possibility of blocking this pathway, perhaps at the SAA1-FPR2 interaction, as a way of treating asthma and other allergic disorders.

The researchers suspect that the newly described SAA1-FPR2 allergic pathway may be relevant not only in asthma and hay fever-type disorders but also in atopic dermatitis (eczema) and food allergies–possibly even in chronic inflammatory disorders such as rheumatoid arthritis and atherosclerosis.

The U.S. Food and Drug Administration approved Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] to mitigate allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts. Treatment with Palforzia may be initiated in individuals ages 4 through 17 years with a confirmed diagnosis of peanut allergy and may be continued in individuals 4 years of age and older. Those who take Palforzia must continue to avoid peanuts in their diets.

“Peanut allergy affects approximately 1 million children in the U.S. and only 1 out of 5 of these children will outgrow their allergy. Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Even with strict avoidance, inadvertent exposures can and do occur. When used in conjunction with peanut avoidance, Palforzia provides an FDA-approved treatment option to help reduce the risk of these allergic reactions in children with peanut allergy.”

Palforzia is a powder that is manufactured from peanuts and packaged in pull-apart color-coded capsules for Dose Escalation and Up-Dosing, and in a sachet for maintenance treatment. The powder is emptied from the capsules or sachet and mixed with a small amount of semisolid food – such as applesauce, yogurt, or pudding – that the patient then consumes.

More information about this is available in FDA Press Release

A coroner investigating 18 year old Owen Carey’s death called for a national register of “severe food anaphylactic reactions”, after the 18-year-old died after eating buttermilk in a grilled chicken burger. Assistant coroner Briony Ballard said that the allergy rate was, in part, due to a “failure to collect together any learning from these tragedies.”

Despite a general greater awareness of food allergies and a greater distribution of Epi-Pens, the rate of deaths from food allergies “remains static”. Ms Ballard said she was concerned there is “no national register recording the circumstances of these deaths, which could then be analysed and learnt from by allergy specialists.”

Anaphylaxis Campaign said it “whole heartedly supports” calls for a national register, adding: “We believe lessons can and must be learnt from tragic deaths related to anaphylaxis.”  There are also talks of potential laws to improve allergy awareness and standards in restaurants.

This Halloween, teal pumpkins will signal safe treats for trick-or-treaters with food allergies as part of the Teal Pumpkin Project, an awareness initiative jointly supported this year by leading food allergy organizations.

Over the past five years, households from every state have participated in the Teal Pumpkin Project, which encourages people to place a teal pumpkin in front of their home to show they have non-food treats, such as toys, available for children with food allergies and medically-necessary dietary restrictions.

Virtually any food can cause a reaction. Many popular Halloween candies contain nuts, milk, egg, soy or wheat, which are among the most common allergens. Additionally, many miniature candy items do not have labels, so it is difficult to determine whether these items are safe.

Taking part in the Teal Pumpkin Project is simple: paint a pumpkin teal, or buy one at any number of national retailers, and place it on front of your home to show you have non-food treats. Participants can offer treats, such as glow sticks or small toys, as an alternative to candy.

The Teal Pumpkin Project was inspired by a local awareness activity by the Food Allergy Community of East Tennessee.

To learn more and add a participating home to Teal Pumpkin Project map, visit www.tealpumpkinproject.org.

The House of Representatives Standing Committee on Health, Aged Care and Sport has commenced an inquiry into allergies and anaphylaxis in Australia.

The Chair of the Committee, Mr Trent Zimmerman MP, said that allergies were seeing a rapid rise in Australia affecting more than four million Australians.

‘Some will experience a life threatening allergic reaction known as anaphylaxis. Over the last 20 years hospital admissions for anaphylaxis has increased five-fold and has a major impact for so many families, schools and child care centres,’ Mr Zimmerman said.

‘While the cause of the increase in allergies remains uncertain, what is clear is that this is a phenomenon found primarily in wealthier western nations like Australia.

‘Severe allergies can be life threatening and this will be an important opportunity for the Parliament to shine a light on how we can better support those at risk.

‘The Committee will be taking a broad look into the potential and known causes of allergies and anaphylaxis, food and drug allergy management, access and cost of services, as well as treatment and support services,’ Mr Zimmerman said.

‘We’re looking forward to hearing from the public, health professionals, and other organisations on how allergies and anaphylaxis is being handled in the wider community. The Committee will investigate whether there is anything further the Government could be doing to make life easier for people living with allergies and anaphylaxis.’

The Terms of Reference of the inquiry also investigate developments into research and prevention of allergies and anaphylaxis, unscientific diagnosis and treatments being used by some consumers, and the impact of unnecessary drug avoidance due to unconfirmed drug allergies.

Submissions from interested individuals and organisations are invited by Thursday 24 October 2019. The preferred method of receiving submissions is by electronic format lodged online using a My Parliament account.

Further information about the Committee’s inquiry, including the full terms of reference and details on how to lodge a submission is available here Click here:

Thirty-two million Americans have food allergies and new research finds more than a million of them are allergic to sesame.

The study by Northwestern University provided the first up-to-date estimates on the current prevalence of sesame allergy among U.S. children and adults in all 50 states. It was published at the JAMA Network Open journal.

Researchers estimate about .49% of the US population reports having a sesame allergy and .23% had what’s called a “convincing,” or true food allergy, with skin, lung, heart or gastrointestinal symptoms.

The study looked at ongoing regulatory rule-making by the U.S. Food & Drug Administration, which is currently considering whether sesame should be added to the list of key food allergens for which mandatory product labeling is required.

At this time, only the labeling of the top eight allergenic foods/food groups is required: peanuts, milk, shellfish, tree nuts, egg, wheat, soy, and finfish (along with proteins derived from them). A change in policy would align with those in Australia, Europe, New Zealand and Canada, which all have sesame labeling requirements.

Seventh-month-old Lofton Hyde of Baton Rourge, LA. was rushed to the hospital for an anaphylactic reaction after daycare workers dipped his foot in paint for a craft project, paint that apparently had dairy-based ingredients.

His mother Christen Hyde says she had no idea dairy ingredients might show up in craft supplies.

Allergist, Dr. Sandhya Mani, says many parents and caretakers don’t realize how common these ingredients are. Many are not listed on the labels of some craft supplies.
“Children with allergies to milk, wheat, oat, corn, sometimes even soy… these are in multiple arts and crafts projects, including paints, clay, chalk,” Mani explained. She suggests looking for products that list ingredients or are marked allergy-friendly. Mani says it’s a problem that needs to have more awareness brought to it as more kids develop allergies.

Airlines must permit passengers to preboard in order to wipe down seats as a precaution against food allergies, the U.S. Department of Transportation says.

The rule includes adults who have food allergies and parents of children with food allergies.

The decision stems after a complaint was filed, the Department of Transportation says severe allergies should be considered a disability and ruled that American Airlines had violated an act similar to the Americans with Disability Act.

Regulators have reiterated that airlines must offer preboarding to passengers with severe allergies to give them extra time to wipe down seating surfaces.