Milk Allergy Research Articles

Degree of hydrolysis is a poor predictor of the sensitizing capacity of whey- and casein-based hydrolysates in a Brown Norway rat model of cow’s milk allergy

The use of infant formulas (IFs) based on hydrolyzed cow’s milk proteins to prevent cow’s milk allergy (CMA) is highly debated. The risk of sensitization to milk proteins induced by IFs may be affected by the degree of hydrolysis (DH) as well as other physicochemical properties of the cow’s milk-based protein hydrolysates within the IFs. The immunogenicity (specific IgG1 induction) and sensitizing capacity (specific IgE induction) of 30 whey- or casein-based hydrolysates with different physicochemical characteristics were compared using an intraperitoneal model of CMA in Brown Norway rats. In general, the whey-based hydrolysates demonstrated higher immunogenicity than casein-based hydrolysates, inducing higher levels of hydrolysate-specific and intact-specific IgG1. The immunogenicity of the hydrolysates was influenced by DH, peptide size distribution profile, peptide aggregation, nano-sized particle formation, and surface hydrophobicity. Yet, only the surface hydrophobicity was found to affect the sensitizing capacity of hydrolysates, as high hydrophobicity was associated with higher levels of specific IgE. The whey- and casein-based hydrolysates exhibited distinct immunological properties with highly diverse molecular composition and physicochemical properties which are not accounted for by measuring DH, which was a poor predictor of sensitizing capacity. Thus, future studies should consider and account for physicochemical characteristics when assessing the sensitizing capacity of cow’s milk-based protein hydrolysates.

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Analisis Penyebab Rendahnya Asupan Nutrisi Susu Sebagai Pendukung Gaya Hidup Sehat Pada Generasi Z

Indonesia has the advantage of developing the agricultural industry,cattle farming is one of the growing fields of animal husbandry in Indonesia. The most product from cattle farming is milk. In 2020, according to BPS ( Central Bureau of Statistics ), Indonesian people consumed milk still around 16.27 liters per capita per year. Dairy products released by the livestock industry and the people who consume them are still relatively low. Therefore,the purpose of this study is to analyze the causes of the low nutritional value of milk as a supporter of a healthy lifestyle in generation Z. The data were collected using a questionnaire and alnalyzed with a qualitative approach, as well as distributing questionnaires online using Google Froms and obtained 112 Generation Z respondents. Nutritional education may be a factor influencing milk consumption in Generation Z. The benefits and milk allergy. The result of the analysis prove that education about the nutritional value of milk, the price of milk and milk allergies affect Generation Z’milk consumption. While the factor that has no effect is milk variants. From the results of the analysis,it can be concluded that the internal factors that influence are individual habits in consuming milk. While the external factor that influences is the selling price of milk.

Nutritional status and feeding difficulties in children up to 2 years of age with cow's milk allergy.

To assess the nutritional status and incidence of feeding difficulties in Polish children up to 2 years of age with cow's milk allergy (CMA) on cow's milk proteins-free diet. A cross-sectional, multi-center study included children aged 6 months to 2 years with confirmed or suspected (without oral food challenge) diagnosis of CMA on the elimination diet for at least 1 month. The primary outcomes were an assessment of proportion of children with impaired nutritional status (with the weight for length and body mass index (BMI) z-score > 1 and <-1), and feeding difficulties according to the Montreal Children's Hospital Feeding Scale. Children with confirmed and suspected CMA were assessed separately. A 144 children with confirmed CMA and 88 with suspected CMA were included (57 and 78% with multiple food allergies, respectively). Among children with confirmed CMA, one-third (35.5%) of participants had any nutritional status impairment regardless of definition. Among those, most of children had mild malnutrition (10.4 vs. 9%) and possible risk of overweight (11.1 vs. 9.7%; following respectively BMI for age and weight for length z-scores). Only 16.0% of children had feeding difficulties. Feeding difficulties was identified to be a risk factor for moderate malnutrition compared to children without feeding difficulties (odds ratio 10, 95% confidence interval: 4-27). Mild malnutrition and possible risk of overweight are concern in children up to 2 years of age on cow's milk proteins-free diet. Feeding difficulties are less common, however, may affect the nutritional status.

Clinical responses and relapses in omalizumab-assisted desensitization to food in children: long-term evolution in real life

Desensitization (DSZ) or oral tolerance induction is increasingly used in children who do not outgrow their food allergies. Off-label omalizumab (OMZ) is used as adjuvant therapy for those with severe reactions, but there is little information on outcomes when OMZ is withdrawn. The long-term outcome in a group of children with severe milk or egg allergy who had undergone an OMZ-assisted DSZ procedure is here described. Clinical data from 21 children from the time they started DSZ until database closure were retrospectively collected, to assess the appearance of symptoms and response to clinical decisions under real-life conditions. Patients received OMZ before, during, and after the DSZ procedure itself and OMZ was subsequently discontinued. The scheduled treatment protocol had to be changed in almost all patients due to reactions or individual needs. Three of 21 patients had to prematurely abandon the procedure due to DSZ failure. The other 18 patients were able to tolerate the target dose of food, but nine of them developed symptoms when eating the food 1.5 to 6 months after stopping OMZ. These patients underwent a second course of OMZ-assisted DSZ, which was successful in six, but three had a second relapse 3 to 8 months after stopping OMZ and decided to quit. OMZ-assisted DSZ failed in almost a third of patients with severe allergy even after a second course of OMZ, almost 40% had a successful outcome with one course of OMZ, while almost a third required a second course. Relapses of symptoms occurred up to six months after stopping OMZ.

Higher Potential Sensitization of Cow αS1-Casein over Goat αS1-Casein in a Mouse Model due to Enhanced Dendritic Cell Uptake and Activation.

Cow's milk allergy is a common food allergy, with the milk protein αS1-casein being a major allergen. This study aimed to investigate differences in sensitization between cow and goat αS1-CN. Cow and goat αS1-CN were labeled with fluorescent dyes and given to mice sensitized with cholera toxin adjuvant. Both proteins reached immune organs, suggesting no major difference in digestion. However, compared with goat αS1-CN, cow αS1-CN is more readily taken up by dendritic cells, inducing dendritic cell maturation. Furthermore, cow αS1-CN can more effectively induce the generation of Th2 cells, leading to a higher production of specific IgE. In a Caco-2/RBL-2H3 cell model, cow αS1-CN caused more mast cell degranulation and loss of epithelial barrier integrity than goat αS1-CN. In summary, this study found differences in immune responses between cow and goat milk αS1-CN. Cow αS1-CN elicited stronger dendritic cell and Th2 responses, leading to increased mast cell degranulation.

Cow's Milk Allergy May Induce Lipid Metabolism Disorder in BALB/c Mice via Exosomes.

Allergic diseases and lipid-metabolism-disorder-derived diseases are both significant public health issues. Recent studies have shown that exosomes are associated with the course of allergic diseases and are involved in lipid metabolism. In this study, exosomes derived from cow's milk allergic (CMA) mice medially loaded lesser proteins favoring cholesterol metabolism. The levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the serum were increased in the CMA mice, and hepatic lipid deposition was observed in the liver, but these phenomena were improved by inhibiting the exosome release. Specifically, the higher expression of the sterol regulatory element binding factor 2 (SREBP2) protein and HMGCR gene in the liver of CMA mice indicated an increase in cholesterol synthesis. NPC1L1 was also highly expressed in the small intestine of CMA mice, and fecal TC level was decreased, suggesting that the reabsorption of cholesterol was elevated. The biosynthesis of cholesterol, the reverse cholesterol transport (RCT) process, and the synthesis of bile acid in the liver were improved by inhibiting exosome release, as well as the reabsorption of cholesterol in the small intestine. This study has for the first time demonstrated the lipid metabolism disorder caused by CMA, especially the important role of exosomes in food allergies and lipid metabolism.

Evaluation of clinical outcomes of efficacy in food allergen immunotherapy trials, COFAITH EAACI task force.

Food allergy is a global public health problem that until recent years lacked any aetiological treatment supported by academy, industry and regulators. Food immunotherapy (AIT) is an evolving treatment option, supported by clinical practice and industry trial data. Recent AIT meta-analyses have highlighted the difficulty in pooling safety and efficacy data from AIT trials, due to secondary heterogeneity in the study. An EAACI task force (CO-FAITH) initiated by the Paediatric Section was created to focus on AIT efficacy outcomes for milk, egg and peanut allergy rather than in trial results. A systematic search and a narrative review of AIT controlled clinical trials and large case series was conducted. A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient-reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure, but OFC methods suffer from heterogeneity and methodological disparity. This review has identified multiple heterogeneous outcomes related to measuring the efficacy of AIT. Efforts to better standardize and harmonize which outcomes, and how to measure them must be carried out to help in the clinical development of safe and efficacious food allergy treatments.

Molecular Screening of Kenyan Raw Donkey Milk for the Presence of Pathogenic Microorganisms-Preliminary Risk Analysis

Donkey milk (DM) has attracted a lot of attention in the recent past probably due to its functional properties. It has been viewed as a suitable replacement to cow milk especially for children with cow milk allergies because it has properties similar to human breast milk. While its properties have been studied in most parts of the world, there seem to be no available data on the quality of donkey milk in Kenya. This is despite the fact that the milk has gained popularity amongst the locals as a therapeutic food capable of curing various ailments as per the locals’ claims. The presence of disease-causing organisms is a concern when considering the safety of drinking raw and fermented donkey milk. Hence, the aim of this study was to analyze the microbiological quality specifically focusing on pathogens of raw and fermented donkey milk sampled in Kenya using culture dependent methods and 16S rDNA sequencing. Pooled donkey milk samples were sampled from Nakuru and Naivasha towns in Kenya and transported in cooler box in dry ice to Kiel, Germany for analysis. The presence of pathogenic microorganisms was investigated by laboratory procedures according to the relevant routine protocols (MBT). The samples were analyzed for Total viable counts (TVC) and pathogens. The presence of Salmonella and Shigela spp was tested using Xylose Lysine Deoxycholate (XLD) and Salmonella-Shigela (SS) Agar. Pathogenic non-O157 ShigaToxin-producing E.coli (STEC) presence was tested using CHROMagarTM –STEC. Other Escherichia coli were tested using Tryptone Bile X-Glucuronic (TBX) Agar while Campylobacter spp presence was tested using modified cefoperazone charcoal deoxycholate agar (mCCDA) and Karmali agar. The presence of Listeria spp was tested using ALOA® Oxoid-Chromogenic Listeria agar. Salmonella shigella deoxycholate calcium (SSDC) and Oxoid Yersinia Selective Agar (Schiemann’s CIN Agar) agar was used to detect the presence of pathogenic Yersinia enterolitica. All these spp tested negative in both fresh and fermented DM samples. Our results indicate that donkey milk could be safe microbiologically for consumption and more research is needed to verify the health benefits claims. There is also need to do whole genome analysis to capture the microorganisms that cannot be cultured.

Epidemiology of food allergy

Food allergy is very common throughout the world and has become a major public health problem, with 220 million people suffering from it. Food allergy has been disproportionately observed in people from industrialized or Western countries and was previously considered to predominate in the pediatric versus adult population. However, the current exponential growth of the adult population and older adults, especially in Western countries, and environmental and lifestyle changes, have profoundly changed the epidemiology of food allergy, with a growing increase even at advanced ages. The foods that represent the greatest severity and clinical impact are peanuts, walnuts, fish, shellfish, eggs, cow's milk protein, wheat, soy and seeds. Although some types of food allergies (cow's milk and egg) may disappear, peanut and tree nut allergies may persist into adulthood. The control or cure of cow's milk protein allergy is gradual throughout childhood and adolescence. Despite the predominance of allergy to fish, shellfish, peanuts, and tree nuts in most reactions in adults, the most common form of IgE-mediated food allergy is oral allergy syndrome or pollen allergy syndrome. food.

Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow's milk allergy.

IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. We report a longitudinal invivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. Invitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes. During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through invitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation. Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.

Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.

Serum levels of specific IgE to cow's milk and its components as predictors of anaphylaxis in Chinese children with cow's milk allergy.

Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis. To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis. This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models. This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis. High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.

A Lipopolysaccharide-Enriched Cow's Milk Allergy Microbiome Promotes a TLR4-Dependent Proinflammatory Intestinal Immune Response.

We have previously reported that the gut microbiota of healthy infants harbors allergy-protective bacteria taxa that are depleted in infants with cow's milk allergy (CMA). Few reports have investigated the role of the gut microbiota in promoting allergic responses. In this study we selected a CMA-associated microbiota with increased abundance of Gram-negative bacteria for analysis of its proinflammatory potential. LPS is the major component of the outer membrane of Gram-negative bacteria. Colonization of mice with a global or conditional mutation of the LPS receptor TLR4 with this CMA microbiota induced expression of serum amyloid A1 (Saa1) and other Th17-, B cell-, and Th2-associated genes in the ileal epithelium in a TLR4-dependent manner. In agreement with the gene expression data, mice colonized with the CMA microbiota have expanded populations of Th17 and regulatory T cells and elevated concentrations of fecal IgA. Importantly, we used both antibiotic-treated specific pathogen-free and germ-free rederived mice with a conditional mutation of TLR4 in the CD11c+ compartment to demonstrate that the induction of proinflammatory genes, fecal IgA, and Th17 cells is dependent on TLR4 signaling. Furthermore, metagenomic sequencing revealed that the CMA microbiota has an increased abundance of LPS biosynthesis genes. Taken together, our results show that a microbiota displaying a higher abundance of LPS genes is associated with TLR4-dependent proinflammatory gene expression and a mixed type 2/type 3 response in mice, which may be characteristic of a subset of infants with CMA.

Expert consensus on diagnosis and management of neonatal cow's milk protein allergy (2023)

Expert consensus on diagnosis and management of neonatal cow's milk protein allergy (2023)

Measurement of oxidative stress-related markers in gastro-intestinal damages in Bulgarian pediatric patients

Cow's milk allergy (CMA), affects ~2 - 7.5% of the infants, and results in an immunological response to casein and α-/β-lactalbumins such as: skin rashes, respiratory and gastrointestinal disturbances. Inflammatory bowel disease (IBD), affecting adolescents, is sustained by an impaired immune/ inflammatory response against intestinal microorganisms. Reactive oxygen/nitrogen (ROS/RNS) overproduction in the gastrointestinal tract damages the mucosa in CMA and IBD. The aim of the present study was to determine ROS/RNS and oxidative disturbances in the intestinal mucosa influence in CMA and IBD. We investigated the levels of advanced protein (OPC), protein carbonyls (PCC), nitric oxide (•NO) and total antioxidant capacity (TAC) in blood serum in CMA and IBD patients. The results showed a significant increase in PCC (p &lt; 0.0001), OPC (p &lt; 0.0001), and increased •NO deposition (p &lt; 0.001) and TAC (p &lt; 0.0001) that likely induce oxidative damage in CMA versus IBD patients. In conclusion, the ROS/RNS accumulation, and oxidative damage to the protein skeleton in the colonic mucosa play a key role in the CMA and IBD pathophysiology, especially in the initiation, duration and maintenance of mucosal inflammation.

Impacts of people at-risk of either cow milk allergies or lactose intolerance on their daily calcium intake and bone mineral density.

People who are at risk of either cow milk allergies or lactose intolerance may need to avoid consuming milk and milk products, which are well-known abundant sources of calcium (Ca). This limitation in calcium intake could affect bone health. Currently, there is limited knowledge on the impact of avoiding the consumption of milk and milk products on the daily Ca intake and bone mineral density (BMD) of people at risk of cow milk allergies. This study aimed to investigate the differences between the amount of Ca intake and BMD values between people who are at risk of cow milk allergies and those who are not. A total of 80 participants were recruited, and further divided into two groups, the at-risk cow milk allergies (AR) group (n = 40) and the normal (NOR) group, using the cow milk allergies and lactose intolerance screening questionnaire. The anthropometric assessment, body composition analyses, 3-day dietary record, and bone mass density (wrist and ankle bones) measurement of all participants were collected using the dual x-ray absorptiometry (DEXA) technique to compare the differences of variables between the two groups. The participants in the AR group presented a significantly lower amount of Ca intake (317 mg/day) than those in the NOR group (623 mg/day) (p < 0.05). The bone mineral density (BMD) parameters indicated that the NOR group presented significantly higher T-scores and BMD values of the wrist (T-score = -0.27 and BMD = 0.57 g/cm2) and ankle (T-score = -0.01 and BMD = 0.59 g/cm2) bones when compared with the AR group (T-score = -1.96 and BMD = 0.48 g/cm2 for the wrist bone, and T-score = -1.18 and BMD = 0.47 g/cm2 for the ankle bone) (p < 0.05). In addition, the results indicated significantly positive correlations between the amount of Ca intake and the T-scores and BMD values of both the wrist and ankle bones among all participants (p < 0.05). In this responding sample, participants at risk of cow milk allergies experienced a significantly negative impact on the amount of Ca intake and BMD values. Professionals in nutrition and dietetics should provide nutrition education and strategies that can enhance the Ca intake among this population to help them meet the daily Ca intake recommendation, ultimately leading to better bone health.

Mexican consensus on cow's milk protein allergy.

The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Risk factors of food sensitization in young children with atopic dermatitis.

Atopic dermatitis (AD) is a common chronic and relapsing skin disease in children and food allergies have been well documented in one-third of children. However, there are limit data about the risk factors of food sensitization in children with AD. The aim of this study was to evaluate the risk factors associated with food sensitization, among AD children. A cross-sectional study, from the electronic medical records of 119 AD patients, aged from 2 to 5 years were reviewed. The demographic data, onset and severity of AD, family history of atopy, age of first antibiotic usage, age of first applying and frequency of moisturizer used, age of introduction to allergenic foods and food specific IgE levels were recorded. The prevalence of food sensitization was; 60%. The most common food allergens were egg white (56.8%), cow's milk (40%) and wheat (34.7%). The significant factors associated with overall food sensitization were; history of parent-reported food allergies (OR = 4.4, P = 0.001), severe AD (OR = 4.5, P = 0.03) and breast feeding > 6 months (OR = 3.5, P = 0.002). Factors associated with egg white allergies were the history of parent-reported food allergies (OR = 3.8, P = 0.02), and severe AD (OR = 4.2, P = 0.04). There were also significant factors associated with cow's milk allergies this being; severe AD (OR = 6, P = 0.03) and a maternal history of asthma (OR = 10.9, P = 0.01). Severe AD was a factor associated with all food sensitization, egg allergy and cow's milk allergy. Maternal asthma was also significantly associated with cow's milk allergy.

Blockade of exosome release alleviates the hypersensitive reaction by influencing the T helper cell population in cow's milk allergic mice.

The aim of this work was to evaluate the ameliorative effects of exosome biogenesis in cow's milk allergy (CMA) response. In this context, BALB/c mice were systemically sensitized with cow's milk proteins plus an aluminum adjuvant to induce CMA. The inhibitor GW4869 of exosome biogenesis was added before sensitization and then the anaphylactic reactions were evaluated both in vivo (clinical score and body temperature) and in vitro (serum histamine, allergen-specific antibodies, cytokines by ELISA and cell analysis by flow cytometry) to explore the role of exosomes in the development of CMA. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) showed that the size distribution and morphology of CMA-derived exosomes were not changed after GW4869 preconditioning, and the concentration of exosomes was much lower than that of the CMA group. In the GW4869 group, inhibition of release of exosomes modulated the induction of T helper 2 cell (Th2)-related substances, with a decrease in histamine and allergen-specific immunoglobulin (Ig) E, and the expression of Th1, Th2, and Th17 cells all decreased as well. Moreover, the experimental data were integrated by means of principal component analysis (PCA) to give an overview that the percentage of Th cells and concentrations of cytokines were more influenced by GW4869 treatment. These data for the first time demonstrated that exosomes are involved in the development of CMA and the blockade of exosome release with GW4869 suppressed the IgE-mediated immune response in CMA.