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.

[Infant gastroesophageal reflux disease: physiological or pathological ?] / Reflux gastrooesophagien du nourrisson : physiologique ou pathologique ?

INFANT GASTRO-ESOPHAGEAL REFLUX DISEASE: PHYSIOLOGICAL OR PATHOLOGICAL ? Gastroesophageal reflux (GER) is defined by the rise of gastric contents into the esophagus, with or without externalization. GER is very common in young infants, with a peak around 4 months, and most often physiological due to high milk intakes and inappropriate relaxation of the lower esophageal sphincter. Evoking a GER disease (GERD) is not always obvious due to signs of poor specificity (crying, irritability, regurgitation). On the other hand, one should not miss warning signs evocative of GERD complicated by esophagitis or of recurrent upper respiratory or ENT infections, or even differential diagnoses (cow milk protein allergy, eosinophilic esophagitis, congenital malformations or brain tumours, etc.). The diagnosis of GERD is clinical but investigations can sometimes be discussed like esophagogastroduodenal endoscopy, 24- hour pH-metry, esophagogastroduodenal follow through. The mechanisms of GERD should be clearly explained to parents and physiological GER should be treated with non-drug measures (adaptation of milk intakes/volumes, thickeners). In the absence of improvement, avoidance of cow's milk proteins for 2 to 4 weeks can be proposed, or even treatment with proton pump inhibitors.

REFLUX GASTRO-OESOPHAGIEN DU NOURRISSON: PHYSIOLOGIQUE OU PATHOLOGIQUE ? Le reflux gastro-oesophagien (RGO) est défini par la remontée du contenu gastrique dans l'oesophage, avec ou sans extériorisation. Le RGO est très fréquent chez le nourrisson, avec un pic vers 4 mois. Il est le plus souvent physiologique, en raison d'une alimentation lactée importante et d'une relaxation inappropriée du sphincter inférieur de l'oesophage. Évoquer un RGO pathologique n'est pas toujours évident, car ses symptômes ont une mauvaise spécificité (pleurs, irritabilité, régurgitations). En revanche, il ne faut pas passer à côté de signes d'alarme évocateurs d'un RGO compliqué par une oesophagite ou par des infections respiratoires hautes ou ORL récidivantes, ni négliger les diagnostics différentiels (allergie aux protéines du lait de vache, oesophagite à éosinophiles, malformations congénitales ou tumeurs cérébrales...). Le diagnostic de RGO est clinique, mais certains examens complémentaires peuvent parfois être discutés : endoscopie oesogastroduodénale, pH-métrie des 24 heures, transit oesogastroduodénal. Il convient de bien expliquer aux parents les mécanismes du RGO et de prendre en charge sa forme physiologique par des mesures non médicamenteuses (adaptation des prises/volumes de lait, épaississants). En l'absence d'amélioration, une éviction des protéines du lait de vache peut être proposée pendant deux à quatre semaines, voire un traitement par inhibiteurs de la pompe à protons.

Oral immunotherapy for Immunoglobulin E-mediated cow's milk allergy in children: A systematic review and meta analysis.

BACKGOUND: 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). CONCLUSION: 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.

Hidrolizada con alto contenido de trigliceridos de cadena media en pacientes pediátricos con linfangiectasia intestinal primaria y alergia a la leche de vaca / Hydrolyzed with high content of medium chain triglycerides in pediatric patients with primary intestinal lymphangiectasia and allergy to cow's milk

ANTECEDENTES En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de la fórmula extensamente hidrolizada con alto contenido de triglicéridos de cadena media en pacientes pediátricos con linfangiectasia intestinal primaria y alergia a la leche de vaca. Así, el Dr. Marco Antonio Morales Acosta, médico especialista en Pediatría del Servicio de Pediatría Especializada del Hospital Nacional Edgardo Rebagliati Martins de la Red Prestacional Rebagliati, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI la solicitud de uso fuera del petitorio del producto fórmula extensamente hidrolizada alta en triglicéridos de cadena media. ASPECTOS GENERALES La linfangiectasia intestinal primaria (LIP) es una enfermedad poco frecuente caracterizada por una dilatación de los vasos linfáticos de la mucosa o submucosa del intestino delgado. Debido a la estasis y, finalmente, a la rotura de los vasos linfáticos, el líquido linfático, rico en albúmina y otras proteínas, se filtra hacia el tracto gastrointestinal (Brownell and Piccoli 2021). La LIP afecta principalmente a niños y adultos jóvenes, y generalmente se diagnostica antes de los 3 años de edad. El síntoma principal es el edema predominantemente bilateral de miembros inferiores relacionado con la gastroenteropatía perdedora de proteínas. También puede haber fatiga, dolor abdominal, pérdida de peso, incapacidad para aumentar de peso, retraso del crecimiento en los niños, diarrea moderada, deficiencias de vitaminas liposolubles debido a malabsorción, o deficiencia de hierro con anemia moderada (Brownell and Piccoli 2021; Orphanet 2021). La etiología y la prevalencia de la LIP es desconocida. En todo el mundo, se han notificado menos de 500 casos (Orphanet 2021). Su diagnóstico se confirma por la observación endoscópica de los vasos linfáticos intestinales dilatados con la correspondiente histología de las muestras de biopsia intestinal (Orphanet 2021). Y los objetivos del tratamiento incluyen maximizar el estado nutricional y la calidad de vida de los pacientes, mediante la reducción de los síntomas y de las secuelas. El pilar de la terapia dietética es una dieta baja en grasas, alta en proteínas y alta en triglicéridos de cadena media (TCM) (Brownell and Piccoli 2021). METODOLOGÍA: Se realizó una búsqueda sistemática utilizando las bases de datos PubMed, Cochrane Library y LILACS. Además, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissáo Nacional de Incorporacáo de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros. Asimismo, se revisó la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en nutrición en pediatría como la North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), la European Society for Clinical Nutrition and Metabolism (ESPEN), y la American Society for Parenteral and Enteral Nutrition (ASPEN). De manera adicional, se hizo una búsqueda en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.qov/) e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/) para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados. Las estrategias de búsqueda para identificar la evidencia de ensayos clínicos aleatorizados (ECA) se encuentran en las Tabla 1, 2 y 3 del Material Suplementario. ANÁLISIS DE LA EVIDENCIA: En la presente evaluación no se identificaron guías, consensos de expertos o estudios que ayudaran a responder la pregunta PICO establecida en este dictamen. En ese sentido la evaluación se centró en la evidencia descrita previamente por el IETSI para el uso de la FEH en niños con APLV y la fórmula con alto contenido de TCM en niños con LIP, la plausibilidad biológica de la eficacia de la intervención de interés, y la opinión de los expertos de EsSalud. CONCLUSIONES: Por todo lo expuesto, el IETSI recomienda el uso de la fórmula extensamente hidrolizada con alto contenido de TCM en pacientes pediátricos con LIP y alergia la leche de vaca. Dado que actualmente el producto farmacéutico fórmula extensamente hidrolizada con alto contenido de triglicéridos de cadena media no cuenta con registro sanitario en el mercado peruano; de requerirse la autorización de este producto farmacéutico se recomienda seguir el procedimiento TUPA 118 "Autorización excepcional para la importación y uso de productos farmacéuticos, dispositivos médicos o productos sanitarios para la prevención y tratamiento individual" en el marco de lo establecido en el artículo 16 de la Ley N° 29459 "Ley de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios".

Long-term outcome of omalizumab-assisted desensitisation to cow’s milk and eggs in patients refractory to conventional oral immunotherapy: real-life study

Background: Oral immunotherapy (OIT) is a promising approach to cow’s milk and egg aller-gies, but reactions are frequent and some patients cannot be desensitized. Objective: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies.Methods: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow’s milk and/or hen eggs refractory to conventional OIT, who under-went OIT with OMZ in our department between 1 January 2010 and 31 December 2015. Results: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5–9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22–33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow’s milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18–37). The median total time with OMZ was 117 weeks (IQR: 88–144). During the OMZ period, 2.44% (1/41) of patients presented anaphy-laxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esoph-agitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7–10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ).Conclusions: Omalizumab allows desensitisation of children with severe allergies to cow’s milk and/or egg without developing severe reactions while receiving this treatment. However, dis-continuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.© 2022 Codon Publications. Published by Codon Publications (AU)

Cow's milk protein ß-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells.

BACKGROUND: Beta-lactoglobulin (BLG) is a bovine lipocalin in milk with an innate defense function. The circumstances under which BLG is associated with tolerance of or allergy to milk are not understood. OBJECTIVE: Our aims were to assess the capacity of ligand-free apoBLG versus loaded BLG (holoBLG) to protect mice against allergy by using an iron-quercetin complex as an exemplary ligand and to study the molecular mechanisms of this protection. METHODS: Binding of iron-quercetin to BLG was modeled and confirmed by spectroscopy and docking calculations. Serum IgE binding to apoBLG and holoBLG in children allergic to milk and children tolerant of milk was assessed. Mice were intranasally treated with apoBLG versus holoBLG and analyzed immunologically after systemic challenge. Aryl hydrocarbon receptor (AhR) activation was evaluated with reporter cells and Cyp1A1 expression. Treated human PBMCs and human mast cells were assessed by fluorescence-activated cell sorting and degranulation, respectively. RESULTS: Modeling predicted masking of major IgE and T-cell epitopes of BLG by ligand binding. In line with this modeling, IgE binding in children allergic to milk was reduced toward holoBLG, which also impaired degranulation of mast cells. In mice, only treatments with holoBLG prevented allergic sensitization and anaphylaxis, while sustaining regulatory T cells. BLG facilitated quercetin-dependent AhR activation and, downstream of AhR, lung Cyp1A1 expression. HoloBLG shuttled iron into monocytic cells and impaired their antigen presentation. CONCLUSION: The cargo of holoBLG is decisive in preventing allergy in vivo. BLG without cargo acted as an allergen in vivo and further primed human mast cells for degranulation in an antigen-independent fashion. Our data provide a mechanistic explanation why the same proteins can act either as tolerogens or as allergens.

DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows' milk allergy in mouse model.

BACKGROUND: Cows' milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow's milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitation in the knowledge of the pathological mechanism underlying CMA, however, the clinical interventions and therapies remain very unsatisfactory. AIM OF THE STUDY: The transcriptional factor FOXP3 possesses crucial roles in CMA, and increased FOXP3 mRNA expression has a predictive function in faster acquisition of tolerance in infants with CMA. But the exact mechanism remains not fully elucidated. METHODS: For PAG treatment, PAG (dissolved in saline 30 mg/mL, 0, 5, 10, 20 mg/kg BW) was administered daily intraperitoneally (ip) for one week at the time that 6 weeks after the CMP sensitisation. RESULTS: In the present study, we revealed that the expression of FOXP3 is significantly up-regulated in PBMCs from CMA patients and CMA mice on mRNA and protein level. Furthermore, a dramatic reduction in the FOXP3 TSDR methylation and a significant increase in the expression of TET2 are observed in CMA patients and CMA mice. More importantly, we found that propargylglycine (PAG) significantly alleviates symptoms of CMA in mice by suppressing the expression of FOXP3 through restoring TET2 expression. CONCLUSIONS: Our work revealed a novel function of PAG on CMA, which may provide a deeper insight into the pathomechanism of CMA and a novel therapy target for CMA clinical interventions.

Oral Immunotherapy for Cow's Milk Allergy: Five Years' Experience from a Single Center in Turkey

Background: Oral immunotherapy for cow's milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions. Aims: To present our experience of oral immunotherapy for cow's milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy. Study Design: Single-center retrospective cohort study. Methods: Forty-two patients with Immunoglobulin-E-mediated cow's milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow's milk were administered until the patient was able to consume 200 mL of cow's milk daily. Results: The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow's milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow's milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis. Conclusion: Oral immunotherapy is a treatment option in patients with cow's milk allergy because of its high efficacy. Adverse reactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow's milk in the skin prick test.

Anaphylaxis to goat/sheep's milk in a 4-year-old boy tolerant to cow's milk.

Immune-mediated reactions to dairy products may vary depending on the mammalian source. We present a case of anaphylaxis to goat/sheep's milk with tolerance to cow's milk. A 4-year-old boy of Eastern European descent presented with gastrointestinal and respiratory symptoms within minutes after eating a goat/sheep's milk-derived food product. The tryptase level measured 1 hour post initial symptoms and 1 month after the allergic reaction were 14.6 µg/L and 5.1 µg/L, respectively (norm: 0.0-13.5 µg/L), confirming the diagnosis of anaphylaxis. A skin prick test performed 1 month after the reaction was highly positive for goat/sheep's milk, but negative for cow's milk. Skin prick tests may establish a life-threatening goat/sheep's milk allergy. Goat/sheep's milk allergy should always be considered in cow's milk-tolerant patients who present with an allergic reaction to dairy products, or when undergoing/have completed of oral immunotherapy for cow's milk allergy.

Infantile Anaphylaxis in Korea: a Multicenter Retrospective Case Study.

BACKGROUND: Anaphylaxis is increasing in young children. The aim of the present study was to analyze the clinical characteristics of anaphylaxis in Korean infants, with a focus on food triggers. METHODS: The study analyzed the medical records of infants aged 0 to 2 years old who had been diagnosed with anaphylaxis in 23 secondary or tertiary hospitals in Korea. RESULTS: We identified 363 cases of infantile anaphylaxis (66.9% male). Cutaneous symptoms were most prevalent (98.6%), followed by respiratory (83.2%), gastrointestinal (29.8%), and neurologic (11.6%) symptoms. Cardiovascular symptoms were noted in 7.7% of the cases. Most of the cases of anaphylaxis (338; 93.1%) were induced by foods. The most common trigger food was cow's milk and cow's milk products (43.8%), followed by hen's eggs (21.9%), walnuts (8.3%), wheat (7.7%), peanuts (4.8%), other nuts (3.0%), and fish (2.1%). In cow's milk-induced anaphylaxis cases, more than half the cases had cow's milk specific immunoglobulin E (sIgE) levels that were lower than the diagnostic decision points (DDPs), which is 5 kUA/L for those under the age of 1 and 15 kUA/L for those over the age of 1. In anaphylaxis induced by hen's egg, most of the cases (91.8%) had hen's egg sIgE levels that were higher than the DDP, which is 2 kUA/L for those under the age of 2 and 7 kUA/L for those over the age of 2. Of the infantile anaphylaxis cases, 46.8% had been treated with epinephrine, and 25.1% had been prescribed an epinephrine auto-injector. CONCLUSION: Cow's milk is the most frequent trigger food of anaphylaxis in Korean infants. However, we found no significant correlation between the sIgE level and clinical severity. Education is required regarding the importance of epinephrine as the first line therapy for anaphylaxis and on properly prescribing epinephrine for infants with a history of anaphylaxis.

Detection of serum and salivary IgE and IgG1 immunoglobulins specific for diagnosis of food allergy.

Given the growing incidence and prevalence of life-threatening food allergies, health concerns have raised new perspectives for in vivo and in vitro diagnostic methodologies, pointing to saliva as a promising material, already used to diagnose other pathologies. Based on the above considerations, this study aimed to verify the possible use of saliva for the detection of IgE and IgG1 in the diagnosis of food allergy. This was a randomized, cross-sectional clinical study with a quantitative approach, developed at a hospital referral center in allergy in the state of Ceará, from January to July 2015. The sample consisted of 36 children of both sexes, aged between 1 and 60 months, with a diagnosis of cow's milk protein allergy (CMPA) by the RAST test. Children hospitalized or under immunosuppressive drugs were excluded from the study. Serum and saliva samples of the participants were collected and subsequently subjected to the indirect immunoenzymatic assay (ELISA) for the detection of specific serum and salivary immunoglobulins for food: corn, papaya, cow's milk, egg white, wheat, soybeans, peanuts, nuts, kiwi, cacao, fish, shrimp, bananas and tomatoes. For comparison of serum and saliva results, the T-test of independent samples and Mann-Whitney were adopted, for samples with normal and non-normal distribution respectively. A confidence interval of 95% was adopted for significant results. It was observed that 100% (n = 36) of the participants presented cow's milk allergy through the indirect ELISA, detecting IgE or IgG1 in serum and saliva. When serum IgE and IgG1 concentrations were compared, there was no statistical difference (p > 0.05) in 12 of the 14 foods evaluated. The same amount (n = 12) of non-significant differences (p > 0.05) was observed in the comparison of the 14 foods under IgE and IgG1 contractions in saliva. In the verification of the average values of IgE present in the serum and saliva of the foods, only cow's milk, fish and papaya showed statistically significant differences (p < 0.05). Of the total food evaluated, only the average levels of IgG1 present in serum and saliva showed a significant value (p < 0.05) in banana and tomato. These findings indicate that the detection of IgE and IgG1 in saliva proves to be as efficient as in the serum. The use of the salivary technique for use in the diagnosis of food allergy is suggested.

Butyrate Enhances Desensitization Induced by Oral Immunotherapy in Cow's Milk Allergic Mice.

BACKGROUND: In previous studies, we showed that a fructo-oligosaccharide- (FOS-) supplemented diet enhanced oral immunotherapy (OIT) efficacy in a mouse model for cow's milk allergy. Fermentation of FOS by intestinal bacteria leads to production of short-chain fatty acids (SCFA) including butyrate. AIM: To investigate the contribution of butyrate in the enhanced efficacy of OIT + FOS. METHODS: C3H/HeOuJ mice were sensitized and received OIT with or without FOS or butyrate supplementation. After treatment, whole blood was collected to conduct a basophil activation test (BAT) and allergen challenges were performed to measure acute allergic symptoms. CD4 + CD25 + regulatory T cells (Tregs) were isolated from treated mice or differentiated in vitro and used in a bone marrow-derived mast cell (BMMC) suppression assay. Cecum content was collected to analyze SCFA concentrations. RESULTS: Allergen-induced basophil activation was reduced in OIT + butyrate samples compared to OIT. Accordingly, the acute allergic skin response and mast cell degranulation upon challenge were reduced in OIT + butyrate and OIT + FOS mice compared to sensitized controls. Butyrate was increased in the cecum content of OIT + FOS mice compared to OIT mice and sensitized controls. Treg-mediated BMMC suppression was enhanced after in vivo butyrate and FOS exposure in combination with OIT but with a more pronounced effect for butyrate. CONCLUSION: Butyrate supplementation enhanced OIT-induced desensitization of basophils and mast cells and Treg functionality. Only OIT + FOS treatment induced potential microbial alterations, shown by increased butyrate levels in cecum content. Both butyrate and FOS are promising candidates to improve OIT efficacy in human studies to treat food allergies.

This is what scientific societies are for. The CIBAL consensus

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The effect of oral immunotherapy treatment in severe IgE mediated milk, peanut, and egg allergy in adults.

INTRODUCTION: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. OBJECTIVE: We aimed to study if OIT is possible in adults. METHODS: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT. The allergy was confirmed with allergen specific IgE tests and oral food challenges (open in milk allergy and double-blind in peanut and egg allergy). The OIT was performed as open. RESULTS: The median dose of protein that led to discontinuation of allergen challenge because of symptoms was 7.5 mg in milk allergy, 25 mg in peanut allergy, and 15 mg in egg allergy. The median period of OIT was 515 days. Currently on OIT are 6/10 milk allergic patients, 4/9 peanut allergic patients and 3/4 egg allergic patients. The median dose of milk protein increased by 60-fold during OIT compared to the allergen challenge dose. In peanut OIT the median dose increased by eightfold and in egg allergy the dose increased with OIT by 35-fold. Local itching was the most common side effect of OIT (73.9% of the patients), four patients reported having used epinephrine autoinjector and three patients having needed emergency room treatment. CONCLUSIONS AND CLINICAL RELEVANCE: OIT can be given in adult patients with severe milk, peanut, or egg allergy only in selected cases. OIT leads into desensitization but it is not clear whether persistent tolerance can be achieved. Mild adverse events during OIT are common.

Cross-over clinical trial for evaluating the safety of camel's milk intake in patients who are allergic to cow's milk protein.

BACKGROUND: Cow's milk protein allergy (CMPA) affects between 0.6 and 0.9% of the general population, and its treatment implies the total elimination of the intake of this protein. Camel's milk has been suggested as an alternative for patients over one year of age who suffer from CMPA due to the difference in the amino acid sequence from that of cow's milk. The objective of this study was to evaluate the safety and tolerability of camel's milk in children with CMPA. METHODS: Crossed clinical trial for the use of camel's milk vs. amino acid formula, carried out at the Dr. Federico Gómez Children's Hospital of Mexico (HIMFG) on patients between one and 18 years of age with diagnosed CMPA confirmed through double-blind, placebo-controlled food challenges (DBPCFCs). Only those whose allergies were confirmed were randomly placed into two groups: those to be administered camel's milk and those to be administered the amino-acid formula for two weeks, followed by a six-week wash-out period, and then a group crossing for a further two weeks. RESULTS: 49 patients with suspected CMPA were included in the study; the diagnosis was confirmed through DBPCFCs in 15 patients, who were those who participated in the study. After having been administered camel's milk, none of the patients presented adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Camel's milk is safe and tolerable in patients above one year of age with CMPA and can be considered as a good alternative given the benefit of its taste compared to other formulas.

Preventive effects of royal jelly against anaphylactic response in a murine model of cow's milk allergy.

CONTEXT: Royal jelly (RJ) has long been used to promote human health. OBJECTIVE: The current study investigated the preventive effects of RJ against the development of a systemic and intestinal immune response in mice allergic to cow's milk proteins. MATERIALS AND METHODS: Balb/c mice treated orally for seven days with RJ at doses of 0.5, 1 and 1.5 g/kg were sensitized intraperitoneally with ß-lactoglobulin (ß-Lg). Serum IgG and IgE anti-ß-Lg were determined by an enzyme-linked immunosorbent assay (ELISA). Plasma histamine levels, symptom scores and body temperature were determined after in vivo challenge to ß-Lg. Jejunums were used for assessment of local anaphylactic responses by an ex vivo study in Ussing chambers and morphologic changes by histological analysis. RESULTS: RJ significantly decreased serum IgG (31.15-43.78%) and IgE (64.28-66.6%) anti-ß-Lg and effectively reduced plasma histamine level (66.62-67.36%) (p < 0.001) at all the doses tested. Additionally, no clinical symptoms or body temperature drops were observed in RJ-pretreated mice. Interestingly, RJ significantly reduced (p < 0.001) intestinal dysfunction by abolishing the secretory response (70.73-72.23%) induced by sensitization and prevented length aberrations of jejunal villi by 44.32-59.01% (p < 0.001). DISCUSSION AND CONCLUSIONS: We speculate that using RJ may help prevent systemic and anaphylactic response in allergic mice. These effects may be related to its inhibitory effects on the degranulation of mast cells.

Functional gastro-intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies.

UNLABELLED: Up to 50% of infants present with symptoms of regurgitation, infantile colic and/or constipation during the first 12 months of life. Although they are often classed as functional disorders, there is an overlap with cows' milk allergy. We present practical algorithms for the management of such disorders, based on existing evidence and general consensus, with a particular focus on primary health care. Management consists of early recognition of warning signs of organic disease, parental reassurance and nutritional strategies. CONCLUSION: The proposed algorithms aim to help healthcare providers manage frequent gastrointestinal and cows' milk-related symptoms in infants safely and effectively.