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1.
Allergy ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899450

RESUMO

BACKGROUND: Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. METHODS: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. RESULTS: CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CONCLUSION: CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

2.
Allergy ; 79(4): 949-963, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38193259

RESUMO

BACKGROUND: 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 ß-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. METHODS: We report a longitudinal in vivo 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. In vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes. RESULTS: 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 in vitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation. CONCLUSION: 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.


Assuntos
Microbiota , Hipersensibilidade a Leite , Humanos , Criança , Pré-Escolar , Bovinos , Feminino , Camundongos , Animais , Disbiose , RNA Ribossômico 16S , Inflamação , Alérgenos , Lactoglobulinas , Imunoglobulina E , Metaboloma
3.
Allergy ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989779

RESUMO

BACKGROUND: Antigen-specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9-specific B cells in oral allergen-specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT. METHODS: Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9-specific B cells were isolated by flow cytometry and RNA-sequencing was performed. Protein profile of Bos d 9-specific B cells was analyzed by proximity extension assay. RESULTS: Increased frequencies of circulating milk allergen Bos d 9-specific B cells were observed after OIT and NT. Milk-desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation-, Breg cells-, BCR-signaling-, and differentiation-related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long-term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen-specific B cells revealed higher levels of regulatory cytokines, IL-10, and TGF-ß after OIT and NT. CONCLUSION: Allergen-specific B cells are essential elements in regulating food allergy towards remission in OIT-received and naturally resolved individuals.

4.
Int Arch Allergy Immunol ; 185(6): 536-544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447540

RESUMO

INTRODUCTION: The primary dietary approach for managing cow's milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. METHODS: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow's milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. RESULTS: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). CONCLUSIONS: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers' growth.


Assuntos
Hipersensibilidade a Leite , Humanos , Hipersensibilidade a Leite/dietoterapia , Hipersensibilidade a Leite/imunologia , Feminino , Masculino , Pré-Escolar , Animais , Criança , Leite/imunologia , Bovinos , Estudos Longitudinais , Lactente , Dieta , Dieta de Eliminação
5.
Pediatr Allergy Immunol ; 35(7): e14202, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39022888

RESUMO

BACKGROUND: The impact of alternative milk substitutes on the nutritional status of children with cow's milk allergy (CMA), the prevailing cause of food allergies, is unresolved. METHODS: A cross-sectional study was performed in children older than 2 years with IgE-mediated CMA. Patients' clinical characteristics, anthropometric measurements, dietary intake (by 3-day food diary), and biochemical markers of nutritional status were assessed. RESULTS: One hundred two children with CMA (68.6% boys; median age, 3.7 years; 51% multiple food allergies) were evaluated. 44.1% of the children consumed plant-based beverages (PBB), 19.6% therapeutic formula and 36.3% did not consume any milk substitutes. In all age groups, dietary calcium, riboflavin, and vitamin D intake of those who did not use milk substitutes were lower than those who consumed formula or PBB (p < .01). Also in the 2-3 years old age group, dietary zinc (p = .011) and iron intake (p = .004) of the formula-fed group was higher. Formula-fed patients had higher levels of 25-OH vitamin D (µg/L) and serum vitamin B12 (ng/L) than PBB-fed patients (respectively; p < .001, p = .005) and those who did not consume any milk substitute (p < .001). Patients of all ages who did not utilize a milk substitute failed to obtain an adequate amount of dietary calcium. CONCLUSION: The use of milk substitutes positively affects dietary calcium, riboflavin, and vitamin D intake in CMA, but their contribution is variable. Those who do not use milk substitutes are at greater risk inadequate of dietary calcium intake. Personalized nutritional advice, given the clinical diversity and the impact of individual differences, is required.


Assuntos
Hipersensibilidade a Leite , Substitutos do Leite , Estado Nutricional , Vitamina D , Humanos , Hipersensibilidade a Leite/dietoterapia , Hipersensibilidade a Leite/imunologia , Feminino , Estudos Transversais , Masculino , Pré-Escolar , Criança , Animais , Vitamina D/sangue , Cálcio da Dieta/administração & dosagem , Riboflavina , Bovinos , Vitamina B 12/sangue
6.
Pediatr Allergy Immunol ; 35(7): e14195, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38989807

RESUMO

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. CONCLUSION: 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.


Assuntos
Imunoglobulina E , Hipersensibilidade a Leite , Proteínas do Leite , Humanos , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/terapia , Estudos Retrospectivos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Feminino , Masculino , Pré-Escolar , Animais , Proteínas do Leite/imunologia , Criança , Lactente , Espanha , Leite/imunologia , Irlanda , Anafilaxia/prevenção & controle , Anafilaxia/imunologia , Anafilaxia/etiologia , Testes Cutâneos , Tolerância Imunológica , Bovinos , Alérgenos/imunologia , Alérgenos/administração & dosagem , Resultado do Tratamento
7.
Pediatr Allergy Immunol ; 35(2): e14084, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38363041

RESUMO

The increasing prevalence of IgE-mediated cow's milk allergy (CMA) in childhood is a worldwide health concern. There is a growing awareness that the gut microbiome (GM) might play an important role in CMA development. Therefore, treatment with probiotics and prebiotics has gained popularity. This systematic review provides an overview of the alterations of the GM, metabolome, and immune response in CMA children and animal models, including post-treatment modifications. MEDLINE, PubMed, Scopus, and Web of Science were searched for studies on GM in CMA-diagnosed children, published before 1 March 2023. A total of 21 articles (13 on children and 8 on animal models) were included. The studies suggest that the GM, characterized by an enrichment of the Clostridia class and reductions in the Lactobacillales order and Bifidobacterium genus, is associated with CMA in early life. Additionally, reduced levels of short-chain fatty acids (SCFAs) and altered amino acid metabolism were reported in CMA children. Commonly used probiotic strains belong to the Bifidobacterium and Lactobacillus genera. However, only Bifidobacterium levels were consistently upregulated after the intervention, while alterations of other bacteria taxa remain inconclusive. These interventions appear to contribute to the restoration of SCFAs and amino acid metabolism balance. Mouse models indicate that these interventions tend to restore the Th 2/Th 1 balance, increase the Treg response, and/or silence the overall pro- and anti-inflammatory cytokine response. Overall, this systematic review highlights the need for multi-omics-related research in CMA children to gain a mechanistic understanding of this disease and to develop effective treatments and preventive strategies.


Assuntos
Microbioma Gastrointestinal , Metaboloma , Hipersensibilidade a Leite , Probióticos , Hipersensibilidade a Leite/imunologia , Humanos , Animais , Microbioma Gastrointestinal/imunologia , Criança , Camundongos , Bovinos , Pré-Escolar , Prebióticos , Modelos Animais de Doenças , Lactente
8.
Pediatr Allergy Immunol ; 35(1): e14065, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284919

RESUMO

As a potential link between genetic predisposition, environmental exposures, and food allergy outcomes, epigenetics has been a molecular variable of interest in ongoing efforts to understand food allergy mechanisms and outcomes. Here we review population-based investigations of epigenetic loci associated with food allergy, focusing on established clinical food allergy. We first provide an overview of epigenetic mechanisms that have been studied in cohorts with food allergy, predominantly DNA methylation but also microRNA. We then discuss investigations that have implemented epigenome-wide approaches aimed at genome-wide profiling and discovery. Such epigenome-wide studies have collectively identified differentially methylated and differentially regulated loci associated with T cell development, antigen presentation, reaction severity, and causal mediation in food allergy. We then discuss candidate-gene investigations that have honed in on Th1, Th2, T regulatory, and innate genes of a priori interest in food allergy. These studies have highlighted methylation changes in specific candidate genes as associated with T regulatory cell activity as well as differential methylation of Type 1 and Type 2 cytokine genes associated with various food allergies. Intriguingly, epigenetic loci associated with food allergy have also been explored as potential biomarkers for the clinical management of food allergy. We conclude by highlighting several priority directions for advancing population-based epigenomic and epigenetic understandings of food allergy.


Assuntos
Hipersensibilidade Alimentar , MicroRNAs , Humanos , Epigenômica , Hipersensibilidade Alimentar/genética , Diferenciação Celular , Epigênese Genética
9.
Pediatr Allergy Immunol ; 35(6): e14163, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825829

RESUMO

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.


Assuntos
Constipação Intestinal , Hipersensibilidade Alimentar , Humanos , Constipação Intestinal/diagnóstico , Constipação Intestinal/terapia , Constipação Intestinal/etiologia , Criança , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/terapia , Pré-Escolar , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Hipersensibilidade a Leite/complicações , Hipersensibilidade a Leite/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Técnica Delphi , Guias de Prática Clínica como Assunto , Lactente , Alérgenos/imunologia , Animais , Prevalência
10.
Pediatr Allergy Immunol ; 35(6): e14174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899602

RESUMO

BACKGROUND: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked-cake/muffin, to develop indirect in-house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients' sera via western blotting (WB) and indirect in-house ELISA. METHOD: A low allergenic product named biscotti-twice baked-cake was developed, and the total protein concentration was determined. The protein content was studied by SDS-PAGE and proteomics. Milk-specific IgE (sIgE) binding assays were performed by WB and indirect in-house ELISA by using patients' sera. RESULTS: Casein band intensity was observed to be lower in the biscotti-twice baked-cake than in the once baked-cake (p = .014). Proteomics analysis and αS1-casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked-cake was shown by WB (p = .0012) and by indirect in-house ELISA (p = .0001). In the ROC analysis, the area under the curve (AUC) of the in-house ELISA IgE was comparable with Uni-CAP milk and casein sIgE. The AUC of the in-house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni-CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively. CONCLUSION: The low allergenicity of the newly developed low allergenic product "biscotti-twice baked-cake" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked-cake/muffin in patients who are reactive to once baked-milk products.


Assuntos
Alérgenos , Dessensibilização Imunológica , Ensaio de Imunoadsorção Enzimática , Imunoglobulina E , Hipersensibilidade a Leite , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/sangue , Alérgenos/imunologia , Feminino , Masculino , Pré-Escolar , Criança , Dessensibilização Imunológica/métodos , Animais , Leite/imunologia , Leite/efeitos adversos , Lactente , Caseínas/imunologia , Proteômica/métodos , Western Blotting , Administração Oral , Adolescente
11.
Curr Allergy Asthma Rep ; 24(3): 121-131, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38416390

RESUMO

PURPOSE OF REVIEW: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. RECENT FINDINGS: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.


Assuntos
Galinhas , Hipersensibilidade Alimentar , Criança , Adolescente , Adulto , Bovinos , Humanos , Pré-Escolar , Feminino , Animais , Adulto Jovem , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Fatores de Risco , Alérgenos/efeitos adversos , Leite
12.
J Pediatr Gastroenterol Nutr ; 78(3): 699-703, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504410

RESUMO

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.


Assuntos
Hipersensibilidade a Leite , Simbióticos , Criança , Feminino , Animais , Bovinos , Humanos , Lactente , Pré-Escolar , Leite , Seguimentos , Aminoácidos , Fórmulas Infantis , Hipersensibilidade a Leite/prevenção & controle , Alérgenos
13.
Eur J Pediatr ; 183(10): 4329-4335, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39078481

RESUMO

The Cow's Milk-related Symptom Score (CoMiSS™) is a scoring system that reflects the appearance and intensity of symptoms possibly related to consumption of cow's milk. The original tool was recently updated by changing the cut-off, and the stool scale and by adding angioedema. There is no data available regarding the natural evolution of CoMiSS in infants with no cow's milk allergy (no-CMA) or a comparison between original and updated CoMiSS values. We determined the original and the updated CoMiSS in infants not diagnosed with cow's milk allergy. The evolution of CoMiSS during the first year of life was assessed repetitively during predefined check-ups at 1.5, 3, 4, 6, 8, 10, and 12 months. The original and updated scores were compared with the Wilcoxon Signed-Rank Test. We also tested the impact of feeding type, age, gender, and order in the family on the CoMiSS. One hundred and twenty-two infants were included. CoMiSS values during the first year of life showed an inverse relation to age. The difference in CoMiSS between the original and updated versions was significant at 6,8,10, and 12 months (p < 0.001), related to the switch from the Bristol Stool Form Scale to the Brussels Infants and Toddlers Stool Scale (BITSS). The difference between both versions of CoMiSS was not significantly different in infants < 6 months (p = 0.999 at 1.5 and 4 months, and p = 0.586 at 3 months, respectively).Conclusion: CoMiSS decreases with age during the first year of life. While there is no difference between the two CoMiSS versions in healthy infants under 6 months of age, the CoMiSS value in the updated version is lower than the original 1 in infants aged 6 to 12 months. What is known? • The Cow's Milk-related Symptom Score (CoMiSS) is a validated awareness tool for cow's milk allergy (CMA). • A CoMiSS of ≥ 10 indicates a risk for cow's milk allergy. What is new? • The natural evolution of CoMiSS in infants not diagnosed with CMA (no-CMA) shows an inverse relation to age. • There is no difference between the original and the updated CoMiSS versions in no-CMA-infants under six months of age, but the updated CoMiSS is lower in infants 6-12 months than the original one.


Assuntos
Hipersensibilidade a Leite , Humanos , Lactente , Hipersensibilidade a Leite/diagnóstico , Feminino , Masculino , Índice de Gravidade de Doença , Recém-Nascido , Animais , Leite/efeitos adversos
14.
Eur J Pediatr ; 183(2): 707-713, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37973640

RESUMO

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0-6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1-Q3) CoMiSS values were 3 (1-5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880).   Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6-12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type.


Assuntos
Hipersensibilidade a Leite , Leite , Lactente , Recém-Nascido , Feminino , Animais , Bovinos , Humanos , Estudos Transversais , Hipersensibilidade a Leite/diagnóstico , Leite Humano , Alérgenos , Fórmulas Infantis
15.
BMC Pediatr ; 24(1): 115, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350893

RESUMO

INTRODUCTION: Cow's milk allergy (CMA) is the most common food allergy in infants. As this food allergy indicates a wide range of clinical syndromes due to immunological reactions to cow's milk proteins, we aimed to evaluate the status of micronutrients in infants suffering from cow's milk allergy. METHODS: In this historical cohort study, infants with CMA were divided into two equal groups: breastfeeding and diet formula feeding. Data were gathered by a form, including the micronutrients such as iron, selenium, calcium, phosphorus, zinc, and vitamin D. Groups were compared and data were analyzed by the IBM SPSS version 21. RESULTS: This study involved 60 six-month-old infants, and the findings revealed no significant difference between the two groups concerning magnesium, phosphorus, zinc, and vitamin D. However, infants in the formula-feeding group exhibited significantly elevated mean serum levels of iron and selenium, whereas breastfed infants displayed higher levels of calcium. CONCLUSION: The findings of this research revealed a significant difference in calcium, selenium, and iron levels between formula-fed and breastfed infants, even though all variables were within the normal range for both groups. In light of these results, conducting further studies with a larger sample size and extended follow-up periods becomes imperative.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Selênio , Lactente , Feminino , Animais , Bovinos , Humanos , Leite Humano , Estudos de Coortes , Micronutrientes , Cálcio , Dieta , Aleitamento Materno , Vitamina D , Ferro , Fósforo , Zinco
16.
Adv Exp Med Biol ; 1449: 79-93, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39060732

RESUMO

The globally dramatic increase in food allergy prevalence and severity is demanding effective preventive and therapeutic strategies. Food allergy derives from a defect of immune tolerance mechanisms. Immune tolerance is modulated by gut microbiome composition and function, and gut microbiome dysbiosis has been associated with the development of food allergy. Selected probiotic strains could regulate immune tolerance mechanisms. The mechanisms are multiple and are still not completely defined. Increasing evidence is providing useful information on the choice of optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge on the crucial role played by postbiotic gut microbiome-derived metabolites, such as butyrate, is also opening the way to a post- biotic approach in the stimulation of immune tolerance.


Assuntos
Disbiose , Hipersensibilidade Alimentar , Microbioma Gastrointestinal , Tolerância Imunológica , Probióticos , Probióticos/uso terapêutico , Humanos , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Hipersensibilidade Alimentar/terapia , Microbioma Gastrointestinal/imunologia , Disbiose/imunologia , Animais
17.
J Dairy Sci ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39343213

RESUMO

Cow milk, although rich in essential nutrients, is a well-known allergic food that can cause allergic reactions in infants and young children. ß-Lactoglobulin accounts for 10% of the total protein in milk and 50% of the whey protein, which has high nutritional value and excellent functional properties but is also the main allergen leading to milk protein allergy. Exploring the mechanism of milk allergy and selecting suitable separation and purification methods to obtain high-purity ß-Lactoglobulin is the premise of research on reducing allergenicity. In this review, the research progress in membrane technology, gel filtration chromatography, ion exchange chromatography, affinity chromatography, precipitation and aqueous 2-phase system separation for the separation and purification of milk ß-Lactoglobulin is reviewed in detail to promote the further development of milk ß-Lactoglobulin separation and purification methods and provide a new method for the development of hypoallergenic dairy products in the future. Among these methods, ion exchange chromatography and gel chromatography are widely used, precipitation is generally used as a crude purification step, and high-performance liquid chromatography and membrane technology are used for further purification to improve the purity of allergens.

18.
J Allergy Clin Immunol ; 152(5): 1196-1209, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37604312

RESUMO

BACKGROUND: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food challenges). OBJECTIVE: We sought to determine whether allergen-specific T cells in CM-allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. METHODS: Using PBMCs from 147 food-allergic pediatric subjects, we mapped T-cell responses to a set of reactive epitopes in CM that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing subjects with CMA from subjects without CMA. We further used the pool to isolate and characterize antigen-specific CD4 memory T cells using flow cytometry and single-cell RNA/TCR sequencing assays. RESULTS: We detected significant changes in the transcriptional program and clonality of CM antigen-specific (CM+) T cells elicited by the pool in subjects with CMA versus subjects without CMA ex vivo. CM+ T cells from subjects with CMA had increased percentages of FOXP3+ cells over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells that have suppressive activity, but CM+ FOXP3+ cells from subjects with CMA showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared with subjects without CMA, suggesting that these are not conventional regulatory T cells. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to use surface markers (CD25, CD127, and CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow-cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from subjects with CMA in an independent cohort, which could be used for diagnostic purposes. Looking specifically for TH2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in subjects with CMA and that had high expression of TH2 cytokines and pathogenic TH2/T follicular helper markers. CONCLUSIONS: Overall, these findings suggest that there are several differences in the phenotypes of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Animais , Bovinos , Feminino , Criança , Humanos , Pré-Escolar , Leite , Epitopos , Alérgenos , Citocinas/metabolismo , Hipersensibilidade Alimentar/complicações , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/complicações , Fatores de Transcrição Forkhead/metabolismo
19.
Compr Rev Food Sci Food Saf ; 23(1): e13257, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284611

RESUMO

Cow milk is a major allergenic food. The potential prevention and treatment effects of lactic acid bacteria (LAB)-fermented dairy products on allergic symptoms have garnered considerable attention. Cow milk allergy (CMA) is mainly attributed to extracellular and/or cell envelope proteolytic enzymes with hydrolysis specificity. Numerous studies have demonstrated that LAB prevents the risk of allergies by modulating the development and regulation of the host immune system. Specifically, LAB and its effectors can enhance intestinal barrier function and affect immune cells by interfering with humoral and cellular immunity. Fermentation hydrolysis of allergenic epitopes is considered the main mechanism of reducing CMA. This article reviews the linear epitopes of allergens in cow milk and the effect of LAB on these allergens and provides insight into the means of predicting allergenic epitopes by conventional laboratory analysis methods combined with molecular simulation. Although LAB can reduce CMA in several ways, the mechanism of action remains partially clarified. Therefore, this review additionally attempts to summarize the main mechanism of LAB fermentation to provide guidance for establishing an effective preventive and treatment method for CMA and serve as a reference for the screening, research, and application of LAB-based intervention.


Assuntos
Produtos Fermentados do Leite , Lactobacillales , Hipersensibilidade a Leite , Animais , Bovinos , Feminino , Alérgenos/análise , Fermentação , Hipersensibilidade a Leite/prevenção & controle , Epitopos
20.
Allergol Int ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39209584

RESUMO

BACKGROUND: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. METHODS: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. RESULTS: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. CONCLUSIONS: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.

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