Immunoproteomics of cow's milk allergy in Mexican pediatric patients.

Immunological mechanisms of non-IgE-mediated cow's milk protein allergy (CMPA) are not well understood. Such a circumstance requires attention with the aim of discovering new biomarkers that could lead to better diagnostic assays for early treatment. Here, we sought both to investigate the mechanism that underlies non-IgE-mediated CMPA and to identify cow's milk immunoreactive proteins in a Mexican pediatric patient group (n = 34). Hence, we determined the IgE and IgG1-4 subclass antibody levels against cow's milk proteins (CMP) by ELISA. Then, we performed 2D-Immunoblots using as first antibody immunoglobulins in the patients'serum that bound specifically against CMP together with CMP enrichment by ion-exchange chromatography. Immunoreactive proteins were identified by mass spectrometry-based proteomics. The serological test confirmed absence of specific IgE in the CMPA patients but showed significant increase in antigen-specific IgG1. Additionally, we identified 11 proteins that specifically bound to IgG1. We conclude that the detection of specific IgG1 together with an immunoproteomics approach is highly relevant to the understanding of CMPA's physiopathology and as a possible aid in making a prognosis since current evidence indicates IgG1 occurrence as an early signal of potential risk toward development of IgE-mediated food allergy. SIGNIFICANCE: Allergies are one of the most studied topics in the field of public health and novel protein allergens are found each year. Discovery of new principal and regional allergens has remarkable repercussions in precise molecular diagnostics, prognostics, and more specific immunotherapies. In this context, specific IgE is widely known to mediate physiopathology; however, allergies whose mechanism does not involve this immunoglobulin are poorly understood although their incidence has increased. Therefore, accurate diagnosis and adequate treatment are delayed with significant consequences on the health of pediatric patients. The study of type and subtypes of immunoglobulins associated with the immunoreactivity of cow's milk proteins together with an immunoproteomics approach allows better comprehension of physiopathology, brings the opportunity to discover new potential cow's milk protein allergens and may help in prognosis prediction (IgG1 occurrence as an early signal of possible risk toward development of IgE-mediated food allergy).

[Physiopathology of food allergies]. / Fisiopatología de la alergia alimentaria.

Food allergy is an adverse reaction to certain foods that have demonstrated "immunological mechanisms"; therefore, this term covers both food allergies mediated or not by immunoglobulin E (IgE). The common pathophysiological mechanism among forms of allergy to foods mediated or not by IgE is found in the failure of clinical and immunological tolerance towards that food. The induction and maintenance of immunological tolerance depends on the active generation of regulatory T cells specific for food antigens. This process is influenced by genetic factors (FOXP3 genes) and epigenetic factors conditioned by the environment (diet, microbiota, and their products). Since the intestinal microbiome can normally promote oral tolerance, current evidence suggests that perturbations of the microbiome may correlate, or even predispose, with food allergy. Understanding the pathogenic mechanism underlying IgE-mediated food allergies allows the implementation of measures aimed at restoring clinical and immunological tolerance. Knowledge of the mechanisms of food allergy will improve the outlook for patients with more severe immediate food allergies and anaphylaxis, as well as those who have comorbidities (atopic dermatitis, eosinophilic esophagitis and EGEIDs).

La alergia alimentaria es una reacción adversa a ciertos los alimentos que han demostrado "mecanismos inmunológicos"; por lo tanto, este término abarca tanto las alergias alimentarias mediadas o no por la inmunoglobulina E (IgE). El mecanismo fisiopatológico común entre las formas de alergia a alimentos mediadas o no por IgE se encuentra en la falla de la tolerancia clínica e inmunológica hacia ese alimento. La inducción y el mantenimiento de la tolerancia inmunológica depende de la generación activa de células T reguladoras específicas para antígenos alimentarios. Este proceso está influenciado por factores genéticos (genes FOXP3) y epigenéticos condicionados por el medio ambiente (dieta, microbiota y sus productos). Puesto que el microbioma intestinal normalmente puede promover la tolerancia oral, la evidencia actual sugiere que las perturbaciones del microbioma pueden correlacionarse, o incluso predisponer, con la alergia alimentaria. Comprender el mecanismo patógeno subyacente a las alergias alimentarias mediadas por IgE permite implementar las medidas destinadas a restaurar la tolerancia clínica e inmunológica. El conocimiento de los mecanismos de la alergia alimentaria mejorará la perspectiva de los pacientes con alergias alimentarias inmediatas más graves y la anafilaxia, además de quienes tienes tienen enfermedades concomitantes (dermatitis atópica, esofagitis eosinofílica y los EGEID).

[Skin test (Skin Prick Test) in food allergy]. / Pruebas cutáneas (Skin Prick Test) en alergia alimentaria.

Skin tests, also known as prick tests, in food allergies are restricted to IgE-mediated food allergies, with results that barely indicate sensitization to a certain food and do not necessarily suggest food allergy. The clinical context of the patient is the decisive point before performing any type of food allergy skin test; Contextualizing and relating the patient's clinical picture with the immunological mechanism of IgE-mediated allergies will allow a better selection of the allergy test for each case. Positive tests should be interpreted more carefully, and consider that during early childhood it is common that several patients may have negative specific serum IgE tests in the blood for food allergens compared to those performed on the skin, which are positive. Skin testing can be carried out with standardized strata of foods, but they are not always available for all foods and some are very unstable. Skin tests can even be performed with raw foods, using the prick to prick technique to perform the puncture with fresh foods (especially fruits or vegetables) or other products that are not commercially available. The skin prick test is a test where, after having placed the allergenic extract in drops or with fresh food itself, the puncture must be carried out with a standardized lancet.

Las pruebas cutáneas, también conocidas como prick test, en alergia alimentaria están restrictas a las alergias a alimentos mediadas por IgE, con resultados que apenas indican sensibilización a cierto alimento y no necesariamente sugieren alergia alimentaria. El contexto clínico del paciente es el punto decisivo antes de realizar cualquier tipo de prueba cutánea de alergia a alimentos; contextualizar y relacionar el cuadro clínico del paciente con el mecanismo inmunológico de las alergias mediadas por IgE permitirá una mejor selección de la prueba de alergia para cada caso. Las pruebas positivas deben interpretarse con más cuidado, y considerar que durante la infancia precoz es común que varios pacientes pueden tener pruebas IgE séricas especificas negativas en sangre para alérgenos alimentarios comparadas con las realizadas en piel, que resultan positivas. La prueba cutánea puede llevarse a cabo con estratos estandarizados de alimentos, pero no siempre se encuentran disponibles para todos los alimentos y algunos son muy inestables. Incluso pueden realizarse pruebas cutáneas con alimentos in natura, mediante la técnica prick to prick para efectuar la punción con alimentos frescos (especialmente con frutas o vegetales) u otros productos que no estén disponibles comercialmente. El skin prick test es una prueba donde después de haber colocado el extracto alergénico en gotas o con el propio alimento fresco debe llevarse a cabo la punción con una lanceta estandarizada.

Association of atopic diseases and parvovirus B19 with acute lymphoblastic leukemia in childhood and adolescence in the northeast of Brazil.

BACKGROUND: Several factors related to the immune system, such as a history of allergies and virus infections, may be associated with acute lymphoblastic leukemia (ALL). The purpose of this study was to analyze whether the presence of atopic diseases and previous infection with parvovirus B19 and Epstein-Barr virus (EBV) are associated with the development of ALL. METHODS: This case-control study was performed in two tertiary hospitals located in northeastern Brazil. The study population included 60 patients who were diagnosed with non-T-cell ALL using myelogram and immunophenotyping and 120 patients in the control group. Atopy was evaluated via a parent questionnaire and medical records. Total immunoglobulin (Ig)E and IgG levels of parvovirus B19 and EBV were measured in the serum. Logistic regression was performed to assess the association between variables and odds of ALL. RESULTS: We identified a significant inverse association between rhinitis, urticaria and elevated IgE serum levels with ALL. A history of parvovirus B19 infection showed a significant association with this type of cancer [OR (95 % CI) 2.00 (1.94-4.26); P = 0.050]. In logistic regression, the presence of atopy was a protective factor [OR (95 % CI) 0.57 (0.38-0.83); P = 0.004], and the presence of IgG for parvovirus B19 was an important risk factor for ALL [OR (95 % CI) 2.20 (1.02-4.76); P = 0.043]. CONCLUSIONS: These results suggest that atopic diseases and elevated total IgE levels are associated with a potential protective effect on the development of ALL. Previous infection with parvovirus B19 contributed to ALL susceptibility.

Desarrollo de tolerancia oral en niños con alergia a la proteína de leche de vaca: seguimiento de 10 años / Oral tolerance development in children with allergy to cow's milk protein: follow-up of 10 years

Se estima que niños alérgicos desarrollen tolerancia oral durante los primeros años de vida con una dieta de eliminación de lácteos. Determinar el tiempo de desarrollo de tolerancia oral a la proteína de leche de vaca, características clínicas y laboratorio. Estudio prospectivo, seguimiento durante 10 años, de niños con alergia a proteína de leche de vaca. Se indicó dieta de eliminación por 4 semanas con posterior reto. Se solicitó IgE total y específica. Se registro edad y tiempo de dieta al confirmarse la tolerancia. 81 niños, 33/81(40,74%) femeninos y 48/81(59,25%) masculinos, edad promedio de diagnóstico 6,22 meses(rango <1-42). Alergia no mediada IgE 32/81 (39,50%) y alergia mediada IgE 49/81 (60,49%); IgE específica para leche de vaca positivo en 55/81 (67,90%). Diagnóstico por respuesta positiva a la dieta de eliminación en 62/81 (76,54%) y con reto en 19/81 (23,45%). Desarrollaron tolerancia después de 12-18m con dieta, 21/32 (65,62%) con alergia no IgE a los 1,6 años y 23/49 (46,93%) con alergia IgE a los 2,13 años. Los niños restantes toleraron entre 19-24m, a los 2,35 y 2,80 años para la alergia no IgE e IgE respectivamente. Después de 36m, continuaron sin tolerar 5 niños entre ambos grupos con progreso a alergia alimentaria múltiple. El diagnóstico de alergia puede basarse en la respuesta positiva a la dieta de eliminación de lácteos, el reto es necesario en casos inciertos y la tolerancia se alcanza a una edad más temprana en niños con alergia no mediada IgE

It is estimated that allergic children develop oral tolerance in the early years of life with a dairy elimination diet. To determine the time development of oral tolerance to cow's milk protein, clinical and laboratory. A prospective study followed for 10 years, children allergic to cow's milk protein. He said elimination diet for 4 weeks after challenge. Was requested total IgE and specific. Age and time was recorded to confirm diet tolerance. 81 children, 33/81 (40.74%) were female and 48/81 (59.25%) male, average age at diagnosis 6.22 months (range <1-42). IgE-mediated allergy is not 32/81 (39.50%) and IgE-mediated allergy 49/81 (60.49%) specific IgE to cow's milk positive in 55/81 (67.90%). Diagnosis by positive response to the elimination diet in 62/81 (76.54%) and challenge in 19/81 (23.45%). Tolerance developed after 12-18m with diet, 21/32 (65.62%) with non-IgE allergy to 1.6 years and 23/49 (46.93%) with IgE allergy to 2.13 years. The remaining children tolerated between 19-24m, to the 2.35 and 2.80 years for non-IgE allergy and IgE, respectively. After 36m, continued without tolerating 5 children between the two groups with multiple food allergy progress. The diagnosis of allergy can be based on positive response to milk elimination diet, the challenge is necessary in uncertain cases and tolerance is reached at an earlier age in children with IgE mediated allergy is not

Food allergy: a practical update from the gastroenterological viewpoint / Food allergy: a practical update from the gastroenterological viewpoint

OBJETIVOS: Apresentar uma revisão atualizada e crítica sobre alergias alimentares, focando principalmente em tratamento e prevenção. FONTES DOS DADOS: Revisão da literatura publicada obtida através do banco de dados MEDLINE, sendo selecionados os mais atuais e representativos do tema (2000-2006). A pesquisa incluiu os sites da European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) e American Academy of Pediatrics (AAP). SíNTESE DOS DADOS: A prevalência de doenças alérgicas tem aumentado nas últimas décadas e alergia alimentar parece fazer parte desse aumento. Alergia alimentar é muito mais comum em pediatria e apresenta impacto médico, financeiro e social significativos em crianças menores e suas famílias. Tratamento e prevenção da alergia alimentar são desafios maiores do ponto de vista da saúde pública e para as comunidades médica e científica. Há muita informação incorreta e condutas médicas discutíveis nessa área. Apresentamos e discutimos as recomendações publicadas pelos Comitês de Nutrição da ESPGHAN juntamente com a Sociedade Européia Pediátrica de Alergologia e Imunologia Clínica (ESPACI) e AAP. CONCLUSÃO: Excesso de diagnósticos de alergia alimentar é bastante prevalente. Há necessidade de uniformização de definições e procedimentos diagnósticos. O objetivo primário do manejo deve ser o de instituir medidas efetivas de prevenção das alergias alimentares. Há necessidade de métodos precisos para confirmar ou excluir o diagnóstico. Os pacientes necessitam tratamento apropriado através da eliminação de alimentos que causam sintomas, ao mesmo tempo evitando os efeitos adversos nutricionais e o custo de dietas inadequadas.

OBJECTIVE: To present an up-to-date and critical review regarding food allergies, focusing mainly on treatment and prevention. SOURCES: Review of published literature searched on MEDLINE database; those data which were the most up-to-date and representative were selected (2000-2006). The search included the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the American Academy of Pediatrics (AAP). SUMMARY OF THE FINDINGS: The prevalence of allergic diseases has increased over the last decades, and food allergy seems to be part of this increase. Food allergy is much more common in pediatrics and has a significant medical, financial and social impact on young children and their families. Treatment and prevention of food allergy is a major challenge for public health, scientific and medical communities. There is a lot of misinformation and the medical management of this condition is still discussable. We present and discuss the guidelines regarding criteria for the prevention of food allergy and atopic diseases published by the Nutrition Committees of ESPGHAN jointly with the European Society for Pediatric Allergy and Clinical Immunology (ESPACI) and AAP. CONCLUSION: The overdiagnosis of food allergy is quite prevalent. There is a need for standardization of definitions and diagnostic procedures. The primary goal of therapy should be to first establish effective means of preventing food allergies. There is a need for accurate diagnostic methods to confirm or rule out the diagnosis. Patients need appropriate treatment by eliminating foods that cause symptoms, while avoiding the nutritional side effects and the cost of inappropriate diets.