Inflammatory Cells That Suppress Skin Allergic Reactions Identified

MedicalResearch.com Interview with:
elstarNidhi Malhotra PhD

Boston Children’s Hospital
Division of Allergy and Immunology
Senior Scientist at Elstar Therapeutics Inc.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Allergies such as Atopic Dermatitis (AD) are rampant in the industrialized nations. Why are we more predisposed to developing hypersensitive reactions to innocuous proteins (allergens) is not well understood. To gain better understanding and to develop better therapies, we need to first delve deeper into how our immune system regulates homeostasis in tissues such as skin. The main cell types that thwart inflammatory reactions are known as regulatory T cells. These cells are generated in thymus and reside in secondary lymphoid tissues but they are also prominent at tissue sites such as in dermal layer of skin. In this study, I focused on understanding how Tregs resident in skin are distinct from the Tregs in secondary lymphoid organs such as lymph nodes (LNs). I uncovered that functioning of Tregs in skin is underpinned by a distinct set of genes. One main gene that I found to be highly expressed in skin Tregs but not in LN Tregs is Rora, which encodes for the transcription factor ROR alpha (RORa).

This observation was intriguing as previous studies had elucidated the requirement of RORa in the development of inflammatory type-2 innate lymphoid cells (ILC2s) and it has been considered the antagonizing RORa functioning would curb allergic responses. However, I observed that Tregs require RORa to suppress allergic responses. In particular, RORa regulates the expression of a TNF receptor family member DR3, which binds to the cytokine TL1A. TL1A has a role in enhancing suppressive activity of Tregs while also enhancing type-2 cytokine production from ILC2s. Hence, in the absence of DR3 in Tregs, we believe more TL1A is available to ILC2s resulting in unrestrained allergic responses.  Continue reading

Synthetic Folic Acid Metabolites May Be Associated With Food Allergy in Children

MedicalResearch.com Interview with:
Emily Clarke McGowan, MD

Assistant Professor, Allergy/Clinical Immunology
Charlottesville, VA 22908-1355

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Folate (vitamin B9) is available in either the natural or synthetic forms and has been shown to reduce the risk of neural tube defects, like spina bifida, in newborns.  Folic acid, the synthetic form of folate, is widely consumed in the United States in infant formula, supplements, vitamins, and fortified grains.  When folic acid is consumed in high quantities, some of this folic acid does not undergo further metabolism and circulates in the blood as “unmetabolized folic acid” (UMFA).

In this study, we measured total folate, UMFA, and 5-methyltetrahydrofolate (5-MTHF), the main folate metabolite involved in biochemical processes in the body, in a subset of children from the Boston Birth Cohort.

While mean levels of total folate at birth were lower among those who developed food allergy, mean levels of the synthetic folic acid derivative, UMFA, were higher.  There was no association between total folate, 5-MTHF, or UMFA levels in early life and the development of food allergy.  Continue reading

Tick Bites Plus Blood Type Predispose to Red Meat Allergy

MedicalResearch.com Interview with:

Brestoff-Parker

Dr. Brestoff-Parker

Jonathan R. Brestoff-Parker, MD, PhD
PSTP Resident, Clinical Pathology
Department of Pathology & Immunology
Washington University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Red meat allergy is a recently recognized food allergy in which people experience a delayed allergic response about 3-6 hours after eating red meats that contain the allergen alpha-gal.

Red meat allergy is thought to be caused by tick bites which expose humans to alpha-gal, however other factors that contribute to disease risk are not well described. Alpha-gal looks a lot like the B antigen, which is one of the factors that determines blood type. So we wondered whether people with blood types B or AB are protected from getting red meat allergy. We were amazed when we found that patients who make the B antigen (blood types B or AB) are 5 times less likely to have red meat allergy than patients who do not make the B antigen (blood types O or A).  Continue reading

AI Trained Computer Program Can Monitor Health Forums To Detect Adverse Drug Reactions

MedicalResearch.com Interview with:

Kavita Sarin, M.D., Ph.D.

Dr. Sarin

Kavita Sarin, M.D., Ph.D.
Assistant Professor of Dermatology
Stanford University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Drug reactions occur in the majority of patients undergoing cancer therapies. Half of serious drug reactions are detected after market approval which can result in painful complications and interruption in therapy. Post-market drug surveillance platforms such as FDA monitoring rely on medical publications and physician reporting and take time to identify trends. We sought to determine if we could identify trends in patient discussions in internet health forums to more rapidly identify chemotherapeutic drug reactions. We chose skin reactions as a proof-of-principle because patients can more easily describe what they see on their skin.

Julia Ransohoff, a medical student, and Azadeh Nikfarham, an informatics postdoctoral fellow trained a computer to recognize when a patient undergoing anti-cancer treatment with PD-1 antagonists or EGFR-inhibitors described a drug reaction in their internet forum posts.

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Can Probiotics and Fish Oil Supplements During Pregnancy Reduce Childhood Allergies?

MedicalResearch.com Interview with:
Dr Robert Boyle, 
Reader in Paediatric Allergy
Department of Medicine
Imperial College London

MedicalResearch.com: What is the background for this study?

Response: Diet in early life may influence whether or not an infant develops allergies or autoimmune disease. We undertook a project for the UK Food Standards Agency to evaluate the evidence for this.

MedicalResearch.com: What are the main findings? 

Response: We found that a probiotic supplement during the last 2-4 weeks of pregnancy and during breastfeeding may reduce an infant’s chances of developing eczema; and that omega-3 fatty acid supplements taken from the middle of pregnancy (20 weeks gestation) through the first few months of breastfeeding may reduce an infant’s chances of developing food allergy. We also found links between longer duration of breastfeeding and improved infant health, but for most other variations in diet during pregnancy or infancy we did not find evidence for a link with allergies or autoimmune disease.

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Oral Immunotherapy With Omalizmuab Resulted in Faster Food Desensitization

MedicalResearch.com Interview with:

Sandra Andorf PhD Kim and Ping Li Director of Computational Biology Sean N. Parker Center for Allergy and Asthma Research at Stanford University Instructor, Nadeau Lab Department of Medicine, Division of Pulmonary & Critical Care Medicine Stanford University School of Medicine

Dr. Andorf

Sandra Andorf PhD
Kim and Ping Li Director of Computational Biology
Sean N. Parker Center for Allergy and Asthma Research at Stanford University
Instructor, Nadeau Lab
Department of Medicine, Division of Pulmonary & Critical Care Medicine
Stanford University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Food allergies are on the rise in the world. Approximately 15 million Americans have food allergies, which includes around 6 million children. Of people with food allergies, 30-40% are allergic to more than one food and therefore these people have a greater risk for an accidental ingestion resulting in an allergic reaction or anaphylaxis.

Currently there is no FDA approved treatment for food allergies but oral immunotherapy, a treatment in which the patient eats small but slowly increasing doses of their allergen until they can tolerate a specified dose, was shown in research settings to be safe in children and adults for up to 5 foods in parallel.

In this trial, we studied the efficacy and safety of Omalizmuab (an anti-IgE drug) treatment with oral immunotherapy in multifood allergic participants versus placebo with oral immunotherapy for a total of 9 months. We found that 83% of the participants who received Omalizumab could tolerate at least 2 g of at least two different food allergens at the end of the trial compared to 33% of those who received placebo. The participants that received Omalizumab were also desensitized faster, meaning they were on average able to eat 2 g of each of their allergic foods earlier in the treatment. Furthermore, we could show that the use of Omalizumab and the fast updosing is safe.

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Most Homes Harbor Multiple Allergens

MedicalResearch.com Interview with:

Dr. Salo

Dr. Salo

Dr. Pӓivi Salo, PhD Epidemiologist
National Institute of Environmental Health Sciences
NIH

MedicalResearch.com: What is the background for this study?

Response: Indoor allergens are important risk factors for asthma and respiratory allergies. Only a few studies have investigated residential allergen exposures on a national scale; the National Health and Nutrition Examination Survey (NHANES) 2005-2006 is the largest and most comprehensive study to date.

MedicalResearch.com: What are the main findings?

Response: Our findings show that exposure to multiple allergens is common in U.S. homes; over 90% of homes had three or more detectable allergens, and 73% of homes had at least one allergen at elevated levels. The presence of pets and pests contributed strongly to elevated allergen levels. Housing characteristics also mattered – elevated exposure to multiple allergens was more likely in mobile homes, older homes, rental homes, and homes in rural areas. For individual allergens, exposure levels varied greatly with age, sex, race, ethnicity, and socioeconomic status. Differences were also found between geographic locations and climatic conditions.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Understanding factors that affect allergen levels in homes is important because elevated allergen levels can trigger and exacerbate symptoms in people who suffer from asthma and allergies. We hope that our findings provide beneficial information to a wide audience from patients to clinicians, identifying factors that influence levels of exposure to individual and multiple allergens

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: The relationships between allergen exposures, allergic sensitization, and disease are complex. Further research is needed to determine how allergen exposures interact with other environmental and genetic factors that contribute to asthma and allergies.

MedicalResearch.com: Is there anything else you would like to add?

Response: We also compared allergen exposures and previously reported allergic sensitization patterns from this national survey to provide a more complete picture. The allergy focused component in NHANES 2005-2006, which we developed in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Centers for Disease Control and Prevention (CDC), allowed national comparisons for the first time. The observed differences and overlaps reflect the complex nature of the relationships between allergen exposures, allergic sensitization, and disease.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Salo P, Wilkerson J, Rose KM, Cohn RD, Calatroni A, Mitchell HE, Sever ML, Gergen PJ, Thorne PS, Zeldin DC. 2017. Bedroom allergen exposures in US households. J Allergy Clin Immunol; doi: 10.1016/j.jaci.2017.08.033(link is external) [Online 30 November 2017].

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

 

Up To 40% of Food Allergic Adolescents Experience Severe Reactions

MedicalResearch.com Interview with:
“Peanuts” by Daniella Segura is licensed under CC BY 2.0Vicki McWilliam

Murdoch Children’s Research Institute (MCRI)

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Food allergy affects up to 10% of children and 2-3% of adults, and appears to increasing in prevalence. The rise in food allergy prevalence has coincided with increased reports of anaphylaxis. Previous research has shown that adolescents are most at risk of experiencing adverse food reactions and appear to be at higher risk of anaphylaxis fatalities but are an understudied age group in food allergy research.

In a large population representative sample of 10,000 10-14 year olds in Melbourne, Australia we found that alarmingly over 40% had experienced an allergic reaction in the past year and almost 10% reported potentially life threatening reactions. Consistent with other research peanut and tree nuts were the most common trigger foods for reactions and those with nut allergy were most at risk of anaphylaxis. Having more than two food allergies doubled the risk of a food allergic reaction compared to those with a single food allergy. Surprisingly, reactions were found to occur most commonly at home rather than restaurants or school.

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EMSY Gene Linked To Peanut and Other Food Allergies

MedicalResearch.com Interview with:

“Peanuts” by Daniella Segura is licensed under CC BY 2.0

Aida Eslami, Ph.D.
Postdoctoral Research Fellow
Dr. Denise Daley’s research group
Centre for Heart and Lung innovation
Providence Heart + Lung Institute
St. Paul’s Hospital
Vancouver, BC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Peanut allergy and food allergies in general are caused by a combination of both genetic and environmental factors. Currently, the genetic basis of peanut allergy is unclear due to a lack of studies on food related allergies.

Our study was comprised of 850 individuals with peanut allergy from the Canadian Peanut Allergy Registry (CanPAR), and nearly 1,000 individuals without peanut allergy and other food allergies. We looked at over 7.5 million genetic markers through a genome-wide association study (GWAS) to identify genes potentially associated with peanut allergy and other food allergies. Our findings are based on results from the CanPAR in combination with the results from other countries: USA, Australia, Germany and the Netherlands.

We identified a gene that is associated with both peanut allergy and other food allergies. This gene is called c11orf30/EMSY and has previously been shown to be involved in other conditions such as asthma, eczema, and allergic rhinitis.

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How Do Viruses Trigger Cough In Asthmatic Children, Even Without Allergies

MedicalResearch.com Interview with:

Giovanni Piedimonte, MD Steven and Nancy Calabrese Endowed Chair for Excellence in Pediatric Care, Research, and Education Professor & Chair of Pediatrics Cleveland Clinic Lerner College of Medicine Case Western Reserve University

Dr. Piedimonte

Giovanni Piedimonte, MD
Steven and Nancy Calabrese Endowed Chair for Excellence in Pediatric Care, Research, and Education
Professor & Chair of Pediatrics
Cleveland Clinic Lerner College of Medicine
Case Western Reserve University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study proves that asthmatic children already have a hyperactive calcium channel that’s extremely sensitive to environmental triggers.

If these children contract a virus, such as RSV, the hyperactive channel causes more severe symptoms that may require care in a hospital setting.

When a child developed asthma or bronchitis in the past, doctors thought these conditions could only be triggered by environmental allergens. There was no explanation why two out of three children ages five and under who wheeze and cough – and still test negative for allergies.

We needed to explore the mechanisms of the calcium molecule and the epithelial cells, which seem to trigger these symptoms without an allergic reaction. If the molecule’s behavior is producing the cough, we just need to figure out how to control the molecule to properly deactivate the cough mechanism in the asthmatic child

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