Faculty Bibliography

BACKGROUND:Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Symptoms are distinct from IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with Th17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood. OBJECTIVE:To use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions. METHODS:Serum samples were obtained before, during, and after an oral food challenge (OFC) (10 FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate (FDR) adjustment was used for analysis of metabolites. Stomach and duodenal biopsies from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay. RESULTS:A total of 34 metabolites were increased during symptomatic FPIES OFCs compared to asymptomatic subjects, including inosine and urate of the purine signaling pathway. Expression of purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC in FPIES patients. The serotonin metabolite 5-hydroxyindoleacetate was significantly elevated post-reaction. Adenosine stimulation of gastric and duodenal biopsies from non-FPIES donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release. CONCLUSIONS:Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting symptoms by triggering serotonin release from gastric and duodenal mucosa. CLINICAL IMPLICATIONS/CONCLUSIONS:The link between gastrointestinal inflammation and FPIES symptoms via adenosine and serotonin suggests novel therapeutic approaches to FPIES by targeting purinergic receptors.

Wheat is a dietary staple in many cultures as well as a common food allergen. Although not as extensively studied as other forms of oral immunotherapy, the current literature suggests that wheat oral immunotherapy (WOIT) can result in successful desensitization. There has only been one multicenter, double-blind, randomized controlled trial of WOIT, along with several open-label nonrandomized trials. The trials were limited by several factors, including small sample sizes; demographic skew; and heterogeneity in dosing, duration, and outcomes. The majority of WOIT regimens results in desensitization, with literature that indicates that a longer duration and higher dosing may lead to more clinical success. WOIT has been associated with adverse events, including allergic reactions, but these events seem to decrease over time. Study on WOIT is underway, but evidence from trials suggests it can be successful and safe. Further studies will need to optimize dosing protocols to improve efficacy and safety.

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines. We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.
Copyright

Background/UNASSIGNED:The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. Purpose/UNASSIGNED:The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities. Results/UNASSIGNED:The main cow's milk allergens - α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others - may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost. Conclusion/UNASSIGNED:The spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.