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Data de publicació electrònica: 24-03-2023 Includes supplementary materials for the online appendix. Food hypersensitivity (FHS) is common, but little is known about the factors associated with severe reactions, age of onset and whether sensitization persists. This study examines the factors associated with self-reported severe food reactions, onset age and the changes in prevalence of sensitization to foods over time in an adult sample. We used data from adults taking part in the European Community Respiratory Health Survey (ECRHS) III (2010–2014) who provided information on food hypersensitivity, including symptoms, suspected culprit food and onset age (n = 4865). A subsample from six countries had serum food-specific IgE tested for 25 core foods and also in 10 years earlier (ECRHS II). We applied logistic regression and McNemar’s test for analyses. The prevalence of self-reported FHS was 13.5% at ECRHS III. Of those providing information on symptoms (n = 611), 26.4% reported severe reactions. About 80% of 1033 reported food-specific reactions (reported by 596 participants) began after age 15. History of asthma (odds ratio OR 2.12 95% confidence interval CI 1.13–3.44) and a younger age of onset of FHS (OR 1.02, 95% CI 1.01–1.03, per year) were associated with higher risks of a lifetime experience of severe food reactions. In the subsample with IgE tested in both surveys (n = 1612), the overall prevalence of sensitization to foods did not change over 10 years. Our findings support previous observations of more severe food reactions in people with asthma and that most FHS reported by this sample started after age 15. We found no evidence of changes in the prevalence of sensitization to food in adults followed for 10 years. HCYL is supported by the Medical Research Council Centre for Environment and Health. NSI is supported by the Centre for Food and Allergy Research (NHMRC Centre of Research Excellence) PhD scholarship and the Melbourne Children’s LifeCourse top-up PhD scholarship (Royal Children’s Hospital Foundation grant #2018-984). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program.

Anaphylaxis; Food hypersensitivity; Latin America Anafilaxi; Hipersensibilitat alimentària; Amèrica Llatina Anafilaxia; Hipersensibilidad alimentaria; América Latina Background Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective To provide updated and extended data on anaphylaxis in this region. Method An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.

Immunoglobulin G; Anaphylaxis; Casein Inmunoglobulina G; Anafilaxis; Caseína Immunoglobulina G; Anafilaxi; Caseïna

Anaphylaxis is a severe allergic reaction, rapid in onset, and can lead to fatal consequences if not promptly treated. The incidence of anaphylaxis has risen at an alarming rate in past decades and continues to rise. Therefore, there is a general interest in understanding the molecular mechanism that leads to an exacerbated response. The main effector cells are mast cells, commonly triggered by stimuli that involve the IgE-dependent or IgE-independent pathway. These signaling pathways converge in the release of proinflammatory mediators, such as histamine, tryptases, prostaglandins, etc., in minutes. The action and cell targets of these proinflammatory mediators are linked to the pathophysiologic consequences observed in this severe allergic reaction. While many molecules are involved in cellular regulation, the expression and regulation of transcription factors involved in the synthesis of proinflammatory mediators and secretory granule homeostasis are of special interest, due to their ability to control gene expression and change phenotype, and they may be key in the severity of the entire reaction. In this review, we will describe our current understanding of the pathophysiology of human anaphylaxis, focusing on the transcription factors’ contributions to this systemic hypersensitivity reaction. Host mutation in transcription factor expression, or deregulation of their activity in an anaphylaxis context, will be updated. So far, the risk of anaphylaxis is unpredictable thus, increasing our knowledge of the molecular mechanism that leads and regulates mast cell activity will enable us to improve our understanding of how anaphylaxis can be prevented or treated.

Al·lèrgia; Epidemiologia; Proteïna de transferència de lípids Alergia; Epidemiología; Proteína de transferencia de lípidos Allergy; Epidemiology; Lipid transfer protein Background Discovered and described 40 years ago, non-specific lipid transfer proteins (nsLTP) are present in many plant species and play an important role protecting plants from stressors such as heat or drought. In the last 20 years, sensitization to nsLTP and consequent reactions to plant foods has become an increasing concern. Aim The aim of this paper is to review the evidence for the structure and function of nsLTP allergens, and cross-reactivity, sensitization, and epidemiology of nsLTP allergy. Materials and Methods A Task Force, supported by the European Academy of Allergy & Clinical Immunology (EAACI), reviewed current evidence and provide a signpost for future research. The search terms for this paper were “Non-specific Lipid Transfer Proteins”, “LTP syndrome”, “Pru p 3”, “plant food allergy”, “pollen-food syndrome”. Results Most nsLTP allergens have a highly conserved structure stabilised by 4-disulphide bridges. Studies on the peach nsLTP, Pru p 3, demonstrate that nsLTPs are very cross-reactive, with the four major IgE epitopes of Pru p 3 being shared by nsLTP from other botanically related fruits. These nsLTP allergens are to varying degrees resistant to heat and digestion, and sensitization may occur through the oral, inhaled or cutaneous routes. In some populations, Pru p 3 is the primary and sole sensitizing allergen, but many are poly-sensitised both to botanically un-related nsLTP in foods, and non-food sources of nsLTP such as Cannabis sativa, Platanus acerifolia, (plane tree), Ambrosia artemisiifolia (ragweed) and Artemisia vulgaris (mugwort). Initially, nsLTP sensitization appeared to be limited to Mediterranean countries, however more recent studies suggest clinically relevant sensitization occurs in North Atlantic regions and also countries in Northern Europe, with nsLTP sensitisation profiles being broadly similar. Discussion These robust allergens have the potential to sensitize and provoke symptoms to a large number of plant foods, including those which are raw, cooked or processed. It is unknown why some sensitized individuals develop clinical symptoms to foods whereas others do not, or indeed what other allergens besides Pru p 3 may be primary sensitising allergens. It is clear that these allergens are also relevant in non-Mediterranean populations and there needs to be more recognition of this. Conclusion Non-specific LTP allergens, present in a wide variety of plant foods and pollens, are structurally robust and so may be present in both raw and cooked foods. More studies are needed to understand routes of sensitization and the world-wide prevalence of clinical symptoms associated with sensitization to these complex allergens.

Anafilaxi; COVID-19; Polietilenglicol Anafilaxia; COVID-19; Polietilenglicol Anaphylaxis; COVID-19; Polyethylene glycol Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Vaccines often cause adverse events; however, the vast majority of adverse events following immunization (AEFI) are a consequence of the vaccine stimulating a protective immune response, and not allergic in etiology. Anaphylaxis as an AEFI is uncommon, occurring at a rate of less than 1 per million doses for most vaccines. However, within the first days of initiating mass vaccination with the Pfizer-BioNTech COVID-19 vaccine BNT162b2, there were reports of anaphylaxis from the United Kingdom and United States. More recent data imply an incidence of anaphylaxis closer to 1:200,000 doses with respect to the Pfizer-BioNTech vaccine. In this position paper, we discuss the background to reactions to the current COVID-19 vaccines and relevant steps to mitigate against the risk of anaphylaxis as an AEFI. We propose a global surveillance strategy led by allergists in order to understand the potential risk and generate data to inform evidence-based guidance, and thus provide reassurance to public health bodies and members of the public.

Cocoa contains bioactive components, which vary according to genetic and environmental factors. The present study aimed to ascertain the anti-allergic properties of native Peruvian cocoa populations (&ldquo, Blanco de Piura&rdquo, or BPC, &ldquo, Amazonas Peru&rdquo, or APC, &ldquo, Criollo de Monta&ntilde, a&rdquo, or CMC, &ldquo, Chuncho&rdquo, or CCC, and an ordinary cocoa or OC). To do so, after an initial in vitro approach, an in vivo study focused on the induction of an anaphylactic response associated with allergic asthma in Brown Norway rats was carried out. Based on their polyphenol content, antioxidant activity and in vitro effects, the APC and CMC were selected to be included in the in vivo study. Cocoa diets were tested in a model of allergic asthma in which anaphylactic response was assessed by changes in body temperature, motor activity and body weight. The concentration of specific immunoglobulin E (IgE), mast cell protease and leukotrienes was also quantified in serum and/or bronchoalveolar lavage fluid. CMC and OC populations exhibited a protective effect on the allergic asthma rat model as evidenced by means of a partial protection against anaphylactic response and, above all, in the synthesis of IgE and the release of mast cell protease.

Allergic asthma is one of the most common chronic diseases of the airways, however it still remains underdiagnosed and hence undertreated. Therefore, an allergic asthma rat model would be useful to be applied in future therapeutic strategy studies. The aim of the present study was to develop an objective model of allergic asthma in atopic rats that allows the induction and quantification of anaphylactic shock with quantitative variables. Female Brown Norway rats were intraperitoneally sensitized with ovalbumin (OVA), alum and Bordetella pertussis toxin and boosted a week later with OVA in alum. At day 28, all rats received an intranasal challenge with OVA. Anaphylactic response was accurately assessed by changes in motor activity and body temperature. Leukotriene concentration was determined in the bronchoalveolar lavage fluid (BALF), and total and IgE anti-OVA antibodies were quantified in blood and BALF samples. The asthmatic animals&rsquo, motility and body temperature were reduced after the shock for at least 20 h. The asthmatic animals developed anti-OVA IgE antibodies both in BALF and in serum. These results show an effective and relatively rapid model of allergic asthma in female Brown Norway rats that allows the quantification of the anaphylactic response.

Previous studies have demonstrated that cocoa intake decreased Th2 immune-related antibodies in rats. In consequence, we aimed to study in depth this cocoa action, particularly assessing its effect on a rat model of food allergy (FA) and also on an anaphylactic response. The involvement of the intestinal immune system was analyzed to allow the action mechanisms to be investigated. The role of cocoa flavonoids in the anti-allergic properties of cocoa was also established. Brown Norway rats were fed either a reference diet or diets containing conventional cocoa (CC) or non-fermented cocoa (NFC). FA to ovalbumin (OVA) was induced and, later, an anaphylactic response was provoked. As expected, the synthesis of anti-OVA IgE and other Th2-related antibodies was inhibited by CC diet. In addition, the release of mast cell protease II after anaphylaxis was partially prevented by CC, although other variables were not modified. The CC diet also attenuated the increase of some Th2-related cytokines released from mesenteric lymph node and spleen cells, and modulated the intestinal gene expression of molecules involved in allergic response. These results demonstrated the local and systemic influence of CC diet. The effects of the NFC diet were weaker than those of CC, suggesting that cocoa components other than flavonoids play a role in cocoa's action. In conclusion, by acting on intestinal and systemic immune functions, a cocoa-enriched diet in rats exhibited a protective effect against FA and partially against anaphylaxis, making this a food of high interest to the fields of health and immunonutrition.

Perioperative hypersensitivity reactions constitute a first-line problem for anesthesiologists and allergists. Therefore, hospitals should have a consensus protocol for the diagnosis and management of these reactions. However, this kind of protocol is not present in many hospitals, leading to problems with treatment, reporting of incidents, and subsequent etiological diagnosis. In this document, we present a systematic review of the available scientific evidence and provide general guidelines for the management of acute episodes and for referral of patients with perioperative hypersensitivity reactions to allergy units. Members of the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) have created this document in collaboration with members of the Spanish Anesthesia Society (SEDAR). A practical algorithm is proposed for the etiologic diagnosis, and recommendations are provided for the management of hypersensitive patients.

BackgroundFood allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods.ObjectiveThe aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization.MethodsRats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified.ResultsSerum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression.ConclusionsThese results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Actualment, l’estudi de la relació entre nutrició i salut ha comportat que la immunonutrició esdevingui una ciència d’interès creixent. El cacau és un aliment ric en macronutrients (fibra, proteïnes, carbohidrats i lípids), micronutrients (minerals i vitamines) i conté una quantitat relativament elevada de flavonoides. Aquests inclouen majoritàriament els flavan-3-ols, com (-)-epicatequina, (+)-catequina i procianidines, compostos amb capacitat antioxidant i amb efectes antitumorals, en processos neurodegeneratius i sobre el sistema cardiovascular i el sistema immunitari. És per aquest motiu que el cacau s’ha convertit en un aliment amb gran interès com a potencial nutracèutic. L’al·lèrgia alimentària representa un problema de salut important en els països industrialitzats amb elevada prevalença en la població adulta i sobre tot en infants. Els individus afectats presenten una resposta immunitària anòmala quan ingereixen certs aliments o components alimentaris. La seva patogènia inclou la pèrdua de tolerància oral a proteïnes dels aliments i, en la majoria de casos, s’acompanya de la producció d’IgE. Entre les diferents manifestacions clíniques destaquen les alteracions gastrointestinals, les afeccions cutànies i l’anafilaxi, que pot arribar a xoc anafilàctic i comprometre la vida del pacient. En base a aquests antecedents, l’objectiu principal de la tesi ha estat determinar si la capacitat immunomoduladora del cacau podia ser útil per controlar la patogènia de l’al·lèrgia alimentària i establir el paper dels flavonoides en aquest efecte. De forma preliminar, es va desenvolupar un model d’al·lèrgia no alimentària, que va permetre estudiar els efectes d’una dieta enriquida amb cacau convencional sobre la resposta immunitària i establir variables objectives per avaluar la resposta anafilàctica. L’efecte del cacau en el model d’al·lèrgia desenvolupat mitjançant una única immunització intraperitoneal d’ovoalbúmina (al·lergogen), hidròxid d’alumini i toxina de Bordetella pertussis (adjuvants) va revelar, principalment, que el cacau atenuava la síntesi d’anticossos específics relacionats amb la resposta immunitària Th2. D’altra banda, en aquest mateix model, es van quantificar els canvis produïts en l’activitat motora immediatament després de realitzar una provocació oral. D’aquesta manera es va poder establir una variable objectiva per avaluar l’anafilaxi que es correlacionava inversament amb la concentració de proteasa II mastocitària sèrica. Posteriorment es va desenvolupar un model d’al·lèrgia alimentària en rata mitjançant la combinació d’una única immunització intraperitoneal, com la descrita anteriorment, amb l’administració oral de l’al·lergogen catorze dies més tard i durant tres setmanes. Aquest model es caracteritza principalment per l’exacerbació en la síntesi d’anticossos relacionats amb la resposta Th2 (IgE, IgG1, IgG2a) conseqüent a l’inici de l’administració oral i que ja és patent a la primera setmana. A més, la provocació oral dels animals amb al·lèrgia alimentària va provocar un increment de fins a sis vegades de la concentració de proteasa mastocitària II i de la seva expressió gènica a nivell intestinal. Un cop desenvolupat i caracteritzat el model d’al·lèrgia alimentària, es va determinar l’efecte d’una dieta enriquida amb cacau en aquest model. Els animals van rebre una dieta rica en cacau convencional des del moment de la immunització intraperitoneal i fins al final de l’estudi. El cacau va ser capaç de reduir la síntesi d’anticossos específics associats a la resposta tipus Th2, especialment d’isotip IgE. També va inhibir la secreció de citocines de tipus Th2 i, a més, en realitzar una provocació oral, va protegir parcialment de la resposta anafilàctica ja que va disminuir la síntesi i alliberament de la proteasa mastocitària II. Per identificar si els responsables d’aquest efecte eren els flavonoides, es va determinar sobre aquest mateix model d’al·lèrgia alimentària, l’efecte d’una dieta enriquida amb cacau no fermentat, el qual proporcionava principalment flavonoides i menys proporció d’altres components. Els cacau no fermentat va tenir un cert impacte en l’al·lèrgia alimentària però els seus efectes van ser menys potents que els observats amb la dieta enriquida amb cacau convencional. Per tant, a la vista dels resultats obtinguts, es pot concloure que els flavonoides del cacau no són els únics responsables del seu poder modulador en la resposta Th2. En resum, la intervenció nutricional amb una dieta enriquida en cacau en el model d’al·lèrgia alimentària desenvolupat, demostra l’efecte beneficiós d’aquest aliment i li confereix un interès especial en el camp de la immunonutrició com a potencial nutracèutic., Nowadays, immunonutrition has become a very interesting issue of study. Due to cocoa has a relatively high content of flavonoids (mainly flavanols such as epicatechin, catechin and procyanidins), and it has a beneficial role in cardiovascular, chronic inflammation and cancer, cocoa has a potential role in immunonutrition as a nutraceutical. On the other hand, food allergy is an immune disease which is caused by food allergens, and is mainly mediated by IgE. During the past decades has become a major public health in westernized countries with an increasing prevalence. Based on these antecedents, the aim of the present study was to ascertain the effect of a cocoa-enriched diet on a food allergy rat model and also to establish the role of cocoa flavonoids in these effects. As a preliminary study, an allergy model by means of an intraperitoneal immunization with ovalbumin (allergen), aluminum hydroxide and toxin from Bordetella pertussis (adjuvants), was achieved. Using this rat model, a diet with conventional cocoa was tested and animals were orally provoked with the allergen to establish unbiased variables to study an anaphylactic response. The conventional cocoa diet was able to reduce Th2-associated antibodies, mainly specific IgE, and cytokines. The anaphylactic response produced a decrease in the number of animal movements which was inversely correlated with serum mast cell protease release. Then, a food allergy model was set up by means of the combination of only one intraperitoneal immunization (as above) with an oral administration of the allergen, fourteen days later and for three weeks. The model was achieved after the first week of oral gavage as demonstrated by a rise in the synthesis of specific antibodies related with Th2 immune response. Finally, using the food allergy model, a nutritional intervention with cocoa was assay. The animals received a conventional cocoa-enriched diet which was able to reduce the synthesis of Th2-specific antibodies and also partially inhibit the anaphylactic response because the diet produced a reduction in the serum concentration of mast cell protease and a down-regulation of its intestinal gene expression. To establish the role of cocoa flavonoids in this immunomodulation, food allergic animals received a diet containing non fermented cocoa which provided mainly flavonoids and no other cocoa components. Although a certain tendency of protection was detected, the conventional cocoa effect was stronger demonstrating that not only flavonoids are responsible for the protection in front of food allergy, and suggesting that cocoa has a high interest in the field of health and immunonutrition.

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. Supported by MeDALL (Mechanisms of the Development of Allergy, EU FP7 Grant agreement no. 261357)

INTRODUCCIÓN La inmunoterapia oral (ITO) es un tratamiento experimental prometedor para alergia alimentaria, que es una enfermedad prevalente que afecta la salud y la calidad de vida. OBJETIVOS 1. Evaluar eficacia y seguridad de ITO en niños alérgicos a huevo y leche de vaca de 5 a 18 años. 2. Definir fenotipos clínicos de acuerdo al perfil de seguridad observado durante ITO. 3. Analizar la utilidad de los parámetros clínicos e inmunológicos basales para predecir el resultado de seguridad de ITO. 4. Estudiar los parámetros inmunológicos humorales a lo largo del seguimiento, así como su correlación con el perfil de seguridad del tratamiento . MÉTODOS Sujetos: Pacientes de 5 a 18 años afectos de alergia alimentaria mediada por inmunoglobulina E (IgE) a huevo (n= 50) y leche (n= 80) Procedimientos: 1. Determinación basal de parámetros clínicos e inmunológicos. 2. Aplicación de protocolo de ITO a huevo o leche. RESULTADOS 1. Eficacia y seguridad La ITO permitió lograr desensibilización completa en el 73% de alérgicos a leche y en el 54% de alérgicos a huevo. La mayoría de pacientes presentó reacciones adversas por ITO (95% por leche y 90% por huevo). La frecuencia de reacciones fue baja en relación a las dosis administradas (6.6% para leche y 7.6% para huevo) en una mediana de seguimiento de 25 y 18 meses, respectivamente. La mayoría de reacciones fueron leves (grados 1-2). 2. Fenotipos de pacientes de acuerdo al perfil de seguridad de ITO Se identificaron 3 fenotipos: a) Los pacientes cuyas reacciones por ITO cedieron a lo largo del seguimiento, presentaron reacciones infrecuentes y generalmente leves, habiendo logrado desensibilización completa (75% de casos en ITO a leche, 48% en ITO a huevo). En ellos, la ITO se consideró segura y eficaz; b) Los pacientes cuyas reacciones no cedieron durante el seguimiento, presentaron reacciones más frecuentes y más graves, y en su mayoría no habían logrado desensibilización completa (17.5% de casos para leche, 34% para huevo); c) En ITO a huevo, un 18% de pacientes fracasó precozmente por reacciones muy frecuentes y más graves. 3. Utilidad de los parámetros clínicos e inmunológicos basales para predecir la seguridad de ITO a. Los casos de fracaso precoz de ITO a huevo, respecto a quienes pudieron progresar, presentaban niveles basales más elevados de IgE, IgA e IgG4 específicas, formas más graves de asma, así como reacciones más graves y dosis umbrales menores en la prueba de exposición basal. b. Determinados parámetros basales resultaron útiles para predecir la frecuencia, gravedad y persistencia de reacciones en el tiempo: - La IgE específica se correlacionan con la frecuencia, gravedad y persistencia de reacciones. - El prick test se correlaciona con la frecuencia de reacciones y es un factor de riesgo independiente para presentar reacciones grado 4 y más persistentes por ITO a leche. - Reacciones más graves en la prueba de exposición basal se correlacionan con la frecuencia de reacciones y son un factor de riesgo independiente para presentar reacciones más persistentes. - Dosis umbrales más bajas en la prueba de exposición basal se correlacionan con la frecuencia, gravedad y persistencia de reacciones por ITO a leche. - Asma de base más grave se asocia con presentar reacciones grado 4. c. La IgE específica tiene buena rentabilidad diagnóstica para predecir una ITO segura. El punto de corte óptimo para seleccionar pacientes para ITO a leche es IgE específica a caseína inferior a 76.35 kU/L y para ITO a huevo, OVA-sIgE inferior a 6.49 kU/L, que asocian una probabilidad de ITO segura del 93.5% y 79% respectivamente. 4. Evolución de parámetros inmunológicos La IgA específica sérica no se modificó tras 12 meses de ITO a huevo. Prick test e IgE específica disminuyeron tras ITO, mientras que sIgG4 aumentó. Los cambios inmunológicos citados ocurrieron tanto en los niños tratados cuyas reacciones cedieron con el tiempo, como en aquellos que continuaron presentando reacciones durante todo el seguimiento. CONCLUSIONES La ITO permite lograr desensibilización en una amplia proporción de pacientes de 5 a 18 años alérgicos a huevo y leche. Las reacciones adversas por dosis de ITO son comunes. Determinados parámetros clínicos e inmunológicos basales, especialmente la IgE específica, ayudan a identificar los pacientes con alta probabilidad de completar la ITO de forma segura, así como aquéllos que fracasarán precozmente o tendrán reacciones persistentes, frecuentes y más graves. La IgA específica sérica no se modifica tras el tratamiento, mientras que la IgE desciende y la IgG4 aumenta. Los cambios inmunológicos citados no se correlacionan con el perfil de seguridad del tratamiento., BACKGROUND Oral immunotherapy (OIT) is a promising experimental treatment for food allergy. AIMS 1. To evaluate the efficacy and safety of OIT in cow´s milk (CM) and egg allergic children. 2. To define clinical phenotypes according to the OIT safety profile. 3. To analyze the usefulness of baseline clinical and immune parameters to predict OIT safety. 4. To evaluate the evolution of humoral immune parameters and its correlation with safety phenotypes. METHODS Patients aged 5-18 years diagnosed with IgE-mediated CM and egg allergy (N= 80 and 50, respectively). Determination of baseline parameters. OIT protocol implementation. RESULTS 1. Complete desensitization was reached in 73% of CM-OIT and 54% of egg-OIT patients. Most cases experienced OIT-related reactions, which were mainly mild. 2. Three clinical phenotypes were identified based on OIT safety: a) Children whose reactions resolved over time on-OIT experienced infrequent and mainly mild reactions. Most of them had reached complete desensitization. In them, OIT was safe and effective (75% of cases in CM-OIT and 48% in egg-OIT); b) Children who experienced ongoing reactions over the entire period on-OIT had frequent and mainly moderate reactions (17.5% in CM-OIT and 34% in egg-OIT); c) In egg-OIT, 18% of cases required early discontinuation due to frequent and more severe reactions not improved by medication and protocol re-adaptation. 3. Particular baseline parameters were useful to predict OIT safety. Early discontinuation was associated with higher specific IgE, IgG4 and IgA levels, more severe asthma, lower threshold and more severe reactions at baseline challenge. Specific IgE and lower CM threshold correlated with reactions frequency, severity and persistence. Specific IgE showed good diagnostic performance to predict a safe OIT (optimal cut-offs: casein-IgE < 76 kU/L for CM-OIT, ovalbumin-IgE