BACKGROUND: Infant feeding guidelines in Australia changed in 2016 to recommend introduction of common allergy causing foods by age 1 year to prevent food allergy. Although the majority of Australian infants now eat peanut and egg by age 6-months, some still develop food allergy despite introducing allergens early.
OBJECTIVE: We aimed to describe the prevalence of food allergy in a cohort recruited after introducing the nation-wide allergy prevention recommendations; identify characteristics of infants who developed allergy despite early introduction of allergens; and estimate the causal effect of modifiable exposures on food allergy prevalence and whether this differed between infants who were introduced to allergen before or after age 6 months.
METHODS: We recruited a population-based sample of 12-month-old infants in Melbourne, Australia. Infants had skin prick tests to 4 foods and parents completed questionnaires. Infants with evidence of sensitisation were offered oral food challenges. Prevalence estimates were adjusted using inverse probability weighting.
RESULTS: In a cohort of infants (n=1420) where nearly all infants had been introduced to common allergens such as egg, milk and peanut by one-year-of age, the prevalence of food allergy remained high at 11.3% (95% CI 9.6-13.4%). Infants who developed food allergy despite introducing the allergen by age 6-months were more likely to have Asian-born parents. Early-onset moderate/severe eczema was associated with an increased odds of food allergy, irrespective of whether allergens were introduced before or after age 6 months. Among infants who were introduced to peanut ≤6m, antibiotic use by age 6 months was associated with an increased odds of peanut allergy (aOR 6.03 (95%CI 1.15-31.60).
CONCLUSIONS: In a cohort where early allergen introduction was common, the prevalence of food allergy remained high. Infants who developed food allergy despite introducing the respective allergen by 6 months were more likely to have Asian parents and early-onset eczema. New interventions are needed for infants with a phenotype of food allergy that is not amenable to early allergen introduction.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow\'s milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA.
METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow\'s milk.
RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group.
CONCLUSIONS: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow\'s milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

UNASSIGNED: Tolerance Induction Program (TIP) immunotherapy applies machine learning contextualized on immunologic and food protein data sets. TIP has established efficacy toward peanut allergy. This form of treatment demonstrates equal efficacy toward cow\'s milk anaphylaxis. TIP maintains remission outcomes defined as a minimum of 7 days of allergen unresponsiveness to high-dose protein exposures. Furthermore, remission patients openly consume unrestricted amounts of dairy protein.
UNASSIGNED: We sought to assess the rate of decline in specific IgE specific whole and component-resolved diagnostics following 1 year of TIP milk immunotherapy.
UNASSIGNED: The study comprised 214 cow milk anaphylactic children who underwent TIP at the Translational Pulmonary & Immunology Research Center/Food Allergy Institute. Postintervention changes in cow milk specific IgE, component-resolved diagnostics, and specific IgG4 were assessed.
UNASSIGNED: After 1 year of 10-g dairy protein weekly sustained unresponsiveness, eosinophil count decreased from 558.38 to 409.26 cells/μL, the mean cow milk IgE decreased from 16.91 to 9.10 kU/L, the mean boiled cow milk IgE decreased from 12.89 to 6.03 kU/L, the mean Bos D4 decreased from 7.38 to 3.52 kU/L, the mean Bos D5 decreased from 6.79 to 3.16 kU/L, and the mean Bos D8 decreased from 13.55 to 6.62 kU/L. Adverse events were rare.
UNASSIGNED: TIP cow milk immunotherapy significantly reduced cow milk specific IgE and component-resolved diagnostics while increasing specific IgG4 in cow milk anaphylactic children. TIP demonstrates safety and clinical efficacy in cow milk anaphylaxis treatment.

BACKGROUND: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse.
OBJECTIVE: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions.
METHODS: Patients who completed milk OIT and reached a maintenance dose of 200 ml of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and adherence to OIT maintenance protocol.
RESULTS: The cohort consisted of 50 patients. Only 56% of the cohort adhered to protocol, which consisted of ingesting a minimum of 200 ml of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions, as well as a reduced incidence of anaphylaxis, healthcare/ER visits, and epinephrine/antihistamine administration.
CONCLUSIONS: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.

Milk is a good source of nutrition but is also a source of allergenic proteins such as α-lactalbumin, β-lactoglobulin (BLG), casein, and immunoglobulins. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas technology has the potential to edit any gene, including milk allergens. Previously, CRISPR/Cas has been successfully employed in dairy cows and goats, but buffaloes remain unexplored for any milk trait. In this study, we utilized the CRISPR/Cas9 system to edit the major milk allergen BLG gene in buffaloes. First, the editing efficiency of designed sgRNAs was tested in fibroblast cells using the T7E assay and Sanger sequencing. The most effective sgRNA was selected to generate clonal lines of BLG-edited cells. Analysis of 15 single-cell clones, through TA cloning and Sanger sequencing, revealed that 7 clones exhibited bi-allelic (-/-) heterozygous, bi-allelic (-/-) homozygous, and mono-allelic (-/+) disruptions in BLG. Bioinformatics prediction analysis confirmed that non-multiple-of-3 edited nucleotide cell clones have frame shifts and early truncation of BLG protein, while multiple-of-3 edited nucleotides resulted in slightly disoriented protein structures. Somatic cell nuclear transfer (SCNT) method was used to produce blastocyst-stage embryos that have similar developmental rates and quality with wild-type embryos. This study demonstrated the successful bi-allelic editing (-/-) of BLG in buffalo cells through CRISPR/Cas, followed by the production of BLG-edited blastocyst stage embryos using SCNT. With CRISPR and SCNT methods described herein, our long-term goal is to generate gene-edited buffaloes with BLG-free milk.

暂无摘要。

BACKGROUND: Adoption of allergen avoidance diets may increase the risk of nutritional deficiencies and affect growth in children with food allergy (FA). How these dietary restrictions have an impact on diet diversity, a health-promoting eating behavior, remains unclear.
OBJECTIVE: To evaluate diet diversity, dietary intake, and weight status of children with FA.
METHODS: Observational study.
METHODS: One hundred children with immunoglobulin E (IgE)-mediated milk, egg, or nut FA or multiple FAs and 60 children with perennial respiratory allergies (RA) matched as controls, aged 3 to 18 years, were consecutively recruited into the study.
METHODS: Dietary intake and diet diversity (number of different foods consumed/day) were assessed through 4 24-hour recalls. Weight status (underweight, healthy weight, overweight, or obesity) was also evaluated.
METHODS: Chi-squared test and 2-sample independent t test were used to test differences between groups. Adjustment for sex, age, and energy intake was made using linear regression.
RESULTS: The percentage of underweight was higher in children with FA (19.6%) compared with children in the control group (5.1%). Children with FA compared with children in the control group consumed more servings of meat (1.7, 95% CI, 1.6, 1.9 vs. 1.5, 95% CI, 1.3, 1.7 servings/day [Padj = 0.031]). No difference was observed in the diet diversity between the 2 groups (11-12 different foods/day). Within the FA group, children with allergy to milk proteins had lower energy intake from protein, lower intake of calcium, lower consumption of commercially prepared sweets, and higher consumption of eggs, compared with children with nut or egg allergy, but no difference in diet diversity was observed.
CONCLUSIONS: Diet diversity did not differ between children with FA and children with no FA, despite some differences in the intake from specific food groups. However, the higher percentage of underweight in children with FA suggests the need for targeted nutrition intervention as early as possible after FA diagnosis.

暂无摘要。

UNASSIGNED: Cow\'s milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow\'s milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit.
UNASSIGNED: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA.
UNASSIGNED: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders.
UNASSIGNED: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow\'s milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as \"conditional\" following the GRADE approach due to the very low certainty about the health effects based on the available evidence.
UNASSIGNED: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients\' and caregivers\' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

UNASSIGNED: Early supplementation and subsequent discontinuation of cow\'s milk formula (CMF) may increase the risk of cow\'s milk allergy in breast-fed infants, but little is known about the relationship between continuous CMF ingestion and cow\'s milk protein-specific immunoglobulin production.
UNASSIGNED: This study aimed to clarify the aforesaid relationship in cow\'s milk-sensitized infants.
UNASSIGNED: Using data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow\'s milk at age 6 months. We compared the differences in median titers of cow\'s milk-specific IgE, casein-specific IgE, and casein-specific IgG4 levels between participants who continued daily or intermittent CMF ingestion up to age 6 months (the \"continuous group\") and participants who discontinued CMF ingestion before age 6 months (the \"discontinued group\").
UNASSIGNED: From among 462 trial participants, 49 (10.6%) were included in this study (21 in the continuous group and 29 in the discontinued group). The median titer of cow\'s milk-specific IgE was 0.17 kUA/L (interquartile range [IQR] = <0.10 to 0.57) in the continuous group and 0.66 kUA/L (IQR = 0.49-1.18) in the discontinued group (P = .0008). The median titer of casein-specific IgE was <0.10 kUA/L (IQR = <0.10 to 0.15) in the continuous group and <0.10 kUA/L (IQR = <0.10 to 0.37) in the discontinued group (P = .51). The median titer of casein-specific IgG4 was 2.58 mgA/L (IQR = 0.77-6.73) in the continuous group and 0.09 mgA/L (IQR = 0.07-0.13) in the discontinued group (P < .0001).
UNASSIGNED: Continuous CMF ingestion may promote casein-specific IgG4 production in cow\'s milk-sensitized infants.