Infant formulas based on hydrolysed cow\'s milk proteins are used when breastfeeding is not feasible in cow\'s milk allergic infants. Camel milk has been shown to be well-tolerated by the majority of children with cow\'s milk allergy (CMA) and may be a substitute in management of CMA. Here we aimed to evaluate the impact of processing on immunogenicity, sensitising, antibody-binding and cross-reactive capacity of cow\'s and camel milk. Cow\'s and camel milk were processed by means of enzyme hydrolysis or heat treatment. Brown Norway rats were immunised with PBS, non-processed, enzyme hydrolysed or heat-treated cow\'s or camel milk. In vivo tests were performed for evaluation of clinical signs. Blood and faecal samples were analysed for levels and specificity of antibody responses. Cow\'s and camel milk showed similar sensitising capacity. Processing decreased the sensitising capacity of cow\'s milk, yet only enzyme hydrolysis but not heat treatment decreased the sensitising capacity of camel milk. Processing affected the specificity of antibodies raised in the rats, though the effect differed between cow\'s and camel milk. The study showed a low cross-reactivity between cow\'s and camel milk, which was decreased with processing, suggesting that processing of camel milk may improve its usefulness in CMA management.

METHODS: In cases where breast milk is unavailable or inadequate, hydrolyzed infant formula is recommended as the primary alternative. The aim of this study is to assess and compare the allergenicity of two partially hydrolyzed whey-based formulas (PHF-Ws) using serum samples from patients with cow\'s milk allergy (CMA).
RESULTS: LC-MS/MS technology is used to investigate the peptide distribution in both samples. The immunoreactivity of two PHF-Ws in 27 serum samples from 50 Chinese infants (02 years) with CMA is analyzed. The results demonstrate that even with a similar a degree of hydrolysis (DH), primary protein sources, peptides with molecular weights <5 kDa, and differences in the number of residual allergenic epitopes in the hydrolyzed peptide segments can lead to varying immune responses.
CONCLUSIONS: The two PHF-Ws have notably high intolerance rates, exceeding 10% among infants with CMA. Therefore, suggesting that PHF-Ws may not be suitable for infants and children with CMA in China.

Some infants and young children suffer from cow\'s milk allergy (CMA), and have always mainly used hypoallergenic infant formula as a substitute for breast milk, but some of these formulas can still cause allergic reactions. In recent years, it has been found that probiotic nutritional interventions can regulate CMA in children. Scientific and reasonable application of probiotics to hypoallergenic infant formula is the key research direction in the future. This paper discusses the mechanism and clinical symptoms of CMA in children. This review critically ex- amines the issue of how probiotics use intestinal flora as the main vector to combine with the immune system to exert physiological functions to intervene CMA in children, with a particular focus on four mechanisms: promoting the early establishment of intestinal microecological balance, regulating the body\'s immunity and alleviating allergic response, enhancing the intestinal mucosal barrier function, and destroying allergen epitopes. Additionally, it overviews the development process of hypoallergenic infant formula and the research progress of probiotics in hypoallergenic infant formula. The article also offers suggestions and outlines potential future research directions and ideas in this field.

Cow\'s milk allergy (CMA) is common in early childhood and the incidence is increasing. However, its mechanisms of action are still not fully understood due to the range of different clinical symptoms. So far, the development of different mouse models has been the best choice to study the molecular mechanisms triggering allergy. However, the selection of suitable strains for the establishment of animal models truly representative of associated human pathologies is still a challenge. Hence, we focused on both C3H/HeNCrl and BALB/c mice to characterize their susceptibility to CMA. After intraperitoneal sensitization, BALB/c and C3H/HeNCrl strains were challenged with β-lactoglobulin (BLG), and compared in allergic symptoms and active immune response, which assessed by specific antibody production and cytokine release. At first, both groups exhibited anaphylaxis, showed specific BLG-related IgE, Th2 response and seemed both suitable for the development of CMA models. However, a detailed analysis revealed that BALB/c had both stronger humoral and Th2 immune responses, producing more antibodies (IgE and IgG/IgG1/IgG2a), and releasing higher levels of Th2-associated cytokines (IL-4, IL-5, IL-13) compared to C3H/HeNCrl mice. Therefore, BALB/c strain would represent a preferential choice in the establishment of CMA models. This study highlights the subtle differences and major outcomes in the selection of mouse strains for the development of suitable food allergy models.

BACKGROUND: Cow\'s milk allergy (CMA) is the most common allergy in infants that decreases the quality of life of patients and their families. Standard treatment for CMA is the strict avoidance of milk; new treatment strategies such as oral immunotherapy (OIT) have been sought for patients with CMA. We aimed to assess the clinical efficacy and safety of OIT in the treatment of children with immunoglobulin E-mediated CMA (IMCMA).
METHODS: We searched all randomized controlled trials in which OIT is used to treat children with IMCMA from five international electronic databases. We estimated a pooled risk ratio (RR) for each outcome using a Mantel-Haenzel fixed-effects model if statistical heterogeneity was low.
RESULTS: Eleven studies were chosen for meta-analysis, including a total of 469 children (242 OITs, 227 controls). One hundred and seventy-six patients (72.7%) in the OIT were desensitized compared with 49 patients (21.6%) in the control group (RR: 7.35, 95% confidence interval (CI): 2.82-19.13, p < .0001). The desensitization effect of OIT was particularly significant in children over 3 years old (RR: 18.05, 95% CI: 6.48-50.26, p < .00001). Although adverse effects were common, they usually involved mild reactions, but epinephrine use was more common in the OIT group (RR: 7.69, 95% CI: 2.16-27.33, p < .002).
CONCLUSIONS: OIT can lead to desensitization in the majority of individuals with IMCMA, especially in patients over 3 years old. A major problem of OIT is the frequency of adverse events, although most are mild. OIT may be an alternative treatment in the future.

Cow\'s milk allergy is a common food allergy in children. Clinically, cow\'s milk-specific IgE (CM-sIgE) antibody test is often used to diagnose milk allergy. An inexpensive light-initiated chemiluminescence assay (LICA), with fast detection speed and small sample volume demand, has application prospects in the field of quantitative detection of CM-sIgE.
Chemibeads coated with five major milk allergens, serum samples, biotinylated anti-human IgE antibodies, and streptavidin-coated sensibeads constitute a system to establish a LICA method for the quantitative detection of CM-sIgE. A series of experiments were performed to optimize its reaction conditions and evaluated its performance.
The optimal conditions for LICA were 10:4 mass ratio of chemibeads to milk allergen, 20 μg/mL chemibeads, 1.0 μg/mL biotinylated anti-human IgE antibodies and a 1/10 dilution of serum for 30-min incubation. The limit of Quantitation (LoQ) was 0.22 kUA/L. For repeatability, the CV ranged from 3.71% to 8.11%. For intermediate precision, the CV ranged from 4.08% to 14.71%. It was linear within 0.20-18.20 kUA/L. This method did not interfere with common interfering substances and total IgE in serum, and there was no obvious cross-reaction with milk-specific IgG and non-milk-specific IgE.
We have established a method to quantitatively detect CM-sIgE based on light-initiated chemiluminescence assay, which has good analytical performance and could meet the needs of clinical laboratories.

Objective: Cow\'s milk allergy (CMA) is a common allergic disease. Probiotics have been suggested as a treatment for CMA, with Lactobacillus rhamnosus GG (LGG) being one of the important predominant choices. Despite reports on this topic, the effectiveness of application in CMA remains to be firmly established. Methods: To assess the effects of LGG on CMA in children, the PubMed/Medline, Embase, Cochrane Library, and Web of Science databases were searched for studies on LGG in treatment of CMA, which were published in the English language. Results: Ten studies were finally included. Significantly higher tolerability rates favoring LGG over controls were observed [risk ratio (RR), 2.22; 95% confidence interval (CI), 1.86-2.66; I 2 = 0.00; moderate-quality evidence]. There were no significant differences in SCORAD values favoring LGG over the placebo (mean difference, 1.41; 95% CI, -4.99-7.82; p = 0.67; very low-quality evidence), and LGG may have improved fecal occult blood (risk ratio, 0.36; 95% CI, 0.14-0.92; p = 0.03; low-quality evidence). Conclusion: We found that LGG may have moderate-quality evidence to promote oral tolerance in children with CMA and may facilitate recovery from intestinal symptoms. However, this finding must be treated with caution, and more gpowerful RCTs are needed to evaluate the most effective dose and treatment time for children with CMA. Registration number: CRD42021237221.

The detection of allergen-specific IgE is of value for the diagnosis of children\'\'s milk allergy. However, its accuracy will interfere with the presence of high levels of specific IgG in the serum of children with milk allergy. To solve this problem, we established a light-initiated chemiluminescent assay (LICA) based on nanomicrospheres, which neutralized the interference of specific IgG by increasing the amount of antigen coated on the microspheres. The ability of this method to resist IgG interference was confirmed by adding extra specific IgG to the serum of allergic patients. Finally, the positive rate of allergen-specific IgE was increased to 85%, which was better than the indirect ELISA (70%), indicating that this method has certain advantages for the detection of specific IgE in children with milk allergy.

Our previous study has confirmed that Lactobacillus acidophilus KLDS 1.0738 (La KLDS 1.0738) could alleviate β-lactoglobulin (β-Lg)-induced allergic inflammation. This study further explored its molecular regulation mechanism through an in vitro macrophage model. β-Lg-induced macrophages were treated with strains of viable or non-viable L. acidophilus and Toll-like receptor 4 (TLR4) inhibitor or miR-146a inhibitor. Our results revealed that β-Lg stimulation led to the increased expression of TLR4/NF-κB signal pathway in macrophages. Similar to TLR4 inhibitor treatment, La KLDS 1.0738 interventions significantly reduced the allergic inflammation by inhibition of TLR4 pathway, which was superior to the commercial L. acidophilus GMNL-185 strains (La GMNL-185) or the control, especially in living L. acidophilus-treated group. Furthermore, La KLDS 1.0738 strains could remarkably reduce transduction of TLR4 and inflammatory cytokine production, which was closely associated with up-regulation of miR-146a levels. MiR-146a inhibitor attenuated the alleviative effect of La KLDS 1.0738, indicating miR-146a might be a crucial mediator of L. acidophilus strains to reduce β-Lg-induced inflammation in macrophages through TLR4 pathway. In conclusion, these observations highlighted that probiotics might regulate host miRNA levels to down-regulate TLR4/NF-κB-dependent inflammation. PRACTICAL APPLICATIONS: Cow\'s milk allergy (CMA) is one of the most common diseases of food allergy, which has a high prevalence in infants and young children. La KLDS 1.0738 has been shown to be effective in alleviating β-Lg-induced allergic inflammation. Our study further found that treatment with La KLDS 1.0738 could suppress the TLR4/NF-κB signaling pathway via modulating miR-146a expression, thereby reducing the overexpression of downstream inflammatory factors. This study not only elucidates the specific pathway of La KLDS 1.0738 to relieve allergic inflammation, but also provides a new insight into the molecular mechanism for the remission and treatment of CMA by probiotics.

Cow\'s milk allergy is one of the most commonly reported childhood food allergies, with increasing incidence, persistence and severity in many countries across the world. The World Allergy Organization Special Committee on Food Allergy has identified cow\'s milk allergy as an area in need of a rationale-based approach in order to make progress against what it considered an onerous problem, with worldwide public health impact. There is growing interest in the potential role of the gut microbiota in the early programming and development of immune responses and allergy. This discussion paper considers the rationale and available evidence for modulation of the gut microbiota and for the use of synbiotics in the management of infants at risk of, or living with cow\'s milk allergy and summarizes remaining research questions that need to be answered for the development of evidence-based recommendations.