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AIFA Prof Ann Kupa Food Allergy Research Grant

Chief Investigator: A/Prof Rachel Peters, Murdoch Children's Research Institute (MCRI), Melbourne

Research Team: A/Prof Jennifer Koplin (University of Queensland), Dr Vicki McWilliam (MCRI, Royal Children's Hospital), Dr Victoria Soriano, Prof Mimi Tang and Ms Megan Mathers (MCRI)

A/Prof Rachel PetersMelbourne has the highest prevalence of food allergy internationally, affecting 10% of 1-year-old infants and 4.5% of adolescents. Since there is no cure for food allergies in Australia, effective prevention strategies are important in reducing the impact of this common condition. Currently, the recommended prevention strategy at the population level is the early introduction of allergenic foods (such as peanut butter), based on positive results from clinical trials for peanut allergy.

In school-age children, cashew allergy is just as prevalent and severe as peanut allergy but is less likely to be outgrown. Research into effective prevention strategies for cashew allergy is severely lacking and much less is known about the natural history of cashew allergy compared to peanut allergy. Our EarlyNuts study revealed that while 87% of infants were consuming peanuts by the age of 1, only 25% were eating cashews. This highlights the need for public health messages that encourage the early introduction of cashews alongside peanuts.

Our study, EarlyNuts, has shown a significant shift in infant feeding practices over the past decade, with infants being introduced to solid foods earlier and consuming high-calorie foods like eggs and nuts at a younger age and in larger quantities. It is important that we assess whether changing infant feeding practices for food allergy prevention has not had unintended consequences health outcomes, such as growth and obesity.

To do this, the study is conducting a longitudinal follow-up of 1933 infants who were initially recruited at 12 months of age. When these children reach the age of 6, they will undergo assessments to test for food allergy and measure their growth. This project will describe the prevalence and natural history of cashew allergy to age 6 years, assess whether changing infant feeding practices was effective at preventing cashew allergy and assess any potential impact on other health outcomes.

MCRI Population Allergy Team

MCRI Team: from left to right are Grace Darling, Megan Mathers, Victoria Soriano, Rachel Peters, Claire Hogan, Koulla Dionisiou and Isobel Hincapie Gallego

AIFA DBV Technologies Food Allergy Research 

Chief Investigator: Dr Vicki McWilliam, Royal Children’s Hospital, Murdoch Children's Research Institute, Melbourne

Research Team: Prof Kirsten Perrett, A/Prof Rachel Peters, and Dr Tim Brettig (MCRI), Dr Joanne Smart (Royal Children's Hospital) 

Vicki McWilliam Cow’s milk allergy is the most common allergy in early childhood and is increasingly reported as a trigger of severe anaphylaxis. Resolution rates are high, however for those with persistent allergy or until resolution occurs, milk avoidance can pose a significant burden on families and impact growth and nutrition. Up to 85% of those with IgE-mediated milk allergy can tolerate baked milk. Baked milk tolerance status is often established to allow inclusion of foods containing baked milk as this is known to improve quality of life and may assist with tolerance induction to whole milk.

Those considered tolerant to baked milk can still experience severe reactions to whole milk, so progression to the introduction of whole cow’s milk is usually established via supervised food challenges. There have been reports of the successful reintroduction of milk among infants with IgE mediated cow’s milk allergy via home-based “milk ladders”. A “milk ladder” is a graded method of reintroducing whole milk into the diet via low dose processed forms of milk, such as a biscuit or cake and progressing through steps such as cheese, yoghurt and then finally whole cow’s milk. This approach is used widely in non-IgE mediated food allergy for the reintroduction of milk but is not typically recommended for use in IgE mediated food allergy due to the concerns of inducing severe reactions.

The use of a dietitian-led, home-based milk ladders for cow’s milk allergy could revolutionise care for infants with mild-moderate cow’s milk allergy, avoiding long term milk avoidance and reducing reliance on hospital-based allergy appoints and food challenges. Most importantly, this approach has the potential to prevent the development of long-term milk allergy and even lead to cow’s milk allergy resolution. Randomized controlled trials are needed to validate safety and efficacy.

Dr McWilliam hypothesises that home-based graded introduction of milk via a “milk ladder” in the first year of life in those with newly diagnosed IgE-mediated cow’s milk allergy will be safe and promote tolerance of whole cow’s milk by 2 years of age. Her team will aim to assess the impact of a home-based graded introduction of cow’s milk compared to the current practice of cow’s milk avoidance on challenge proven cow’s milk allergy, growth, allergy related health care costs, parental anxiety, and quality of life at 2 years of age.

AIFA CSL Behring Primary Immunodeficiency Clinical Research Grant 

Chief Investigator: Dr Kuang-Chih Hsiao, Starship Children's Hospital, The University of Auckland, New Zealand

Research Team: Dr Maia Brewerton (Auckland City Hospital), Dr Alberto Pinzon Charry (Queensland Children's Hospital), Dr Andrew Wood (Starship Blood and Cancer Centre), Dr See-Tarn Woon (LabPLUS) 

Dr Kuang Chih HsiaoEffective communication is crucial for our immune system to function normally. When a virus invades our body, our immune cells have to be able to receive warning signals communicated from other cells, so that they can respond promptly and efficiently to protect our body. When communication is disrupted, a person can get life-threatening or fatal viral infections. A genetic form of such communication disruption, affecting a crucial receptor of warning signals, is called IFNAR1 deficiency.

Although extremely rare globally, Dr Hsiao's team has found IFNAR1 deficiency to occur more commonly in the Pacific region. To date, doctors and nurses in New Zealand and Australia have diagnosed and looked after a small number of children affected by this rare condition. Despite the best medical care, 60% of these children affected by viral infection with excessive inflammation died.

They believe that the best way to help these children survive and have excellent quality of life is earlier diagnosis, avoidance of viruses where possible, and better diagnosis and treatment of viral infections when they do occur.

Dr Hsiao and his team want to find out which things help patients stay alive at 12 months after being diagnosed with IFNAR1 deficiency. In the meantime, through this project, they will provide doctors in the Oceanian region three important tools that we believe might help improve their patients’ chance of surviving: 1) educational resources to help doctors become better at spotting the warning signs of this condition, 2) more options to help diagnose this condition promptly, including a new, fast and accurate test we have developed, and 3) an evidence-based management guideline describing how to better protect patients against severe viral infections and treat excessive inflammation.

It is hoped that this project will ultimately lead to improved chances of survival for children who have IFNAR1 deficiency in the Oceanian region. 

AIFA Early Career Research Grant 

Chief Investigator: Ms Daniela Ciciulla, Murdoch Children’s Research Institute, Melbourne 

Research Team: A/Prof Jennifer Koplin (University of Queensland), Dr Vicki McWilliam and A/Prof Rachel Peters (MCRI) 

Daniela CiciullaChronic diseases involving strict dietary adherence have been associated with an increased risk of eating disorders (EDs). Our recent systematic review suggested that eating disorders may be more prevalent in individuals with food allergy compared to those without. Eating disorders have an increased risk of premature mortality, a high personal and economic burden and lengthy delays in diagnosis and treatment. However, research is limited exploring risk factors for eating disorders in those living with food allergy. This project aims to identify predictive as well as modifiable factors that increase the risk of eating disorders in individuals with food allergy. This will be the first survey of its kind and will provide valuable insights into factors that can help identify individuals at a higher risk of eating disorders.

This cross-sectional study will involve an Australia wide survey targeted and distributed to youth and young adults with a food allergy (14 - 39 years old) through Allergy & Anaphylaxis Australia (A&AA) and the National Allergy Councils’ 250k Project Facebook page, website and email database. The survey will be designed to be completed in no longer than 20 minutes, will be anonymous and will be accessed via an online link. The potential clinical impact of this study includes reduced overall burden of individuals with food allergy by aiding early detection and treatment of eating disorders when complicated by a food allergy. 

AIFA Early Career Research Grant

Chief Investigator: Dr Logan Gardner, The Alfred Hospital, Melbourne 

Research Team: Dr Priscilla Auyeung, Dr Mark Hew, Dr Celia Zubrinich, and Dr Stephanie Stojanovic (Alfred Health), Dr Graham Mackay (The University of Melbourne) 

Dr Logan GardnerAnaphylaxis is a rapid and severe reaction affecting many parts of the body that can be life-threatening. It is usually caused by allergy to triggers that are familiar such as peanuts or certain medications. Idiopathic cases (where there is no identifiable external allergenic trigger) represent 30-60% of adult presentations. Idiopathic anaphylaxis is a difficult diagnosis for patients to live with as a trigger cannot be avoided, making further events unpredictable.

A different process leading to reactions to certain medications has recently been identified in some patients. It is not known if this new process can also be responsible for other types of allergic reactions, such as when patients develop anaphylaxis for no clear reason. This new process is what our study will explore.

AIFA Early Career Research Grant 

Chief Investigator: Dr Adrian Lee, Westmead Institute for Medical Research, Sydney 

Research Team: A/Prof Joanne Reed (Westmead Institute for Medical Research, University of Sydney), Dr Kha Phan (La Trobe University), Dr Jing Jing Wang (Flinders University), A/Prof Ming-Wei Lin (Westmead Institute for Medical Research, University of Sydney and Westmead Hospital), Prof Tom Gordon (Flinders University, SA Pathology and Flinders Medical Centre).

Dr Adrian LeeDiseases of the immune system that attack itself are known as autoimmune diseases. In Australia, these are quite common (affecting around 1 in 12 people) and can range from affecting a single organ (e.g., the pancreas in type 1 diabetes) to the entire body (e.g., lupus). The origins of autoimmune diseases are still poorly understood and as such, treatments are non-specific and may lead to significant acute and chronic long-term side-effects. These diseases are characterised by blood biomarkers known as autoantibodies – proteins that can “attack” the body’s own proteins.

There are further unmet needs with the diagnosis of these conditions, with patients often experiencing an unnecessarily long delay to diagnosis. This may be, in part, related to the autoantibody biomarkers either being absent completely or when present, non-specific for a particular diagnosis.

This project explores these autoantibody biomarkers and will identify unique molecular signatures that can provide more information on the diagnoses and be used to monitor disease at a patient-specific level. We will also use sequencing technology to identify the immune cells (B cells) that cause these biomarkers and understand why they are turning their attack on itself. Finally, what causes these damaging autoantibodies to form may relate to incompletely removed cellular debris and our project will also examine apoptotic bodies (dying cell debris) which may incite an autoimmune response.

Patients will be recruited from the Western Sydney Lupus Biobank and Western Sydney Sjögren’s Syndrome Biobank (WS3B) which have been specifically set up to facilitate research into these difficult and neglected disorders. We anticipate that our findings will help clinicians better diagnose and monitor patients with autoimmune diseases like lupus and Sjögren’s disease and our preliminary findings have already demonstrated the usefulness of our “bench-to-bedside” approach.

Dr Adrian Lee Research Team

Team members form left to right: Joanne Reed, Adrian Lee, Thanh Huyen Phan, Zhankun Qi, Lara Glass.

AIFA Early Career Research Grant

Chief Investigator: Dr Shruti Swamy, Garvan Institute of Medical Research, Sydney      

Research Team: A/Prof Elissa Deenick, Prof Tri Phan and Mr Aidan Telfsar (Garvan Institute), Dr Peter Hsu (The Children’s Hospital at Westmead) 

Dr Shruti SwamyInborn errors of immunity are genetic conditions that cause those affected to have a dysfunctional immune system. This can lead to problems such as susceptibility to infection, allergy and autoimmunity.

We identified two siblings both of whom developed severe lung disease at a very early age (under 3 years old). We suspected that these two siblings had a genetic cause of their disease, so we undertook genetic testing and examined their whole genome. This identified part of one gene that was missing in both patients suggesting that the lack of this gene was causing the disease in these patients. Lack of this gene has never been described as causing disease before, making this a novel finding. To improve treatment of these patients we need to understand how this gene affects immune cells and causes their lung disease.

To investigate this further we used genetic engineering to make a mouse “avatar” which had the same genetic change as the patients. Using these mice as well as lung and blood cells from the patients we will investigate what changes this genetic deletion causes. Further, we will use our mouse avatars to test whether bone marrow transplant might be able to restore proper immune function and stop the lung damage.

Thus, this project will provide important information not only to provide a diagnosis for these patients and their family but also to identify potential treatments.  It will further add to our genetic database of known genes implicated in inborn errors of immunity.