In search of a tolerance-induction strategy for cow's milk allergies: significant reduction of beta-lactoglobulin allergenicity via transglutaminase/cysteine polymerization

OBJECTIVE: To explore the use of β-lactoglobulin polymerized using microbial transglutaminase and heating to identify whether protein polymerization could reduce in vivo allergenicity and maintain in vitro and ex vivo immunoreactivity for use in tolerance-induction protocols. METHODS: Based on previous protocols applied in mice and children, we performed in vivo challenges (using a skin prick test) with native and polymerized β-lactoglobulin in adult patients with an IgE-mediated allergy to plactoglobulin. In vitro humoral immunoreactivity was analyzed using immunoblotting. Cell-mediated immunoreactivity was analyzed using ex vivo challenges with native and polymerized β-lactoglobulin and monitored by leukocyte adherence inhibition tests. RESULTS: The skin tests demonstrated that there was a significant reduction in immediate cutaneous reactivity after polymerization. Polymerization did not decrease the immunoblotting detection of s-IgE specific to β-lactoglobulin. Cell-mediated immunoreactivity, as assessed by ex vivo challenges and leukocyte adherence inhibition tests, did not exhibit significant differences between leukocytes challenged with native versus polymerized β-lactoglobulin. CONCLUSIONS: The polymerization of β-lactoglobulin decreased in vivo allergenicity and did not decrease in vitro humoral or ex vivo cell-mediated immunoreactivity. Therefore, we conclude that inducing polymerization using transglutaminase represents a promising technique to produce suitable molecules for the purpose of designing oral/ sublingual tolerance induction protocols for the treatment of allergies.

Epidemiología de la alergia alimentaria en la edad pediátria / Epidemiology of food allergy in children

La incidencia de alergia alimentaria (AA) en niños es del 2-8%. Más del 90% de las AA en los lactantes son causados por leche de vaca (LV), huevo de gallina, soya, maní, nueces, trigo, pescado y mariscos. Existen algunos factores de riesgo para el desarrollo de AA. El impacto de la LM sobre el desarrollo de las alergias es controversial. Hay un 0.21% de APLV neonatal. La introducción antes del 4 mes de vida de más de 4 alimentos está asociada con un mayor riesgo de dermatitis atópica. La prueba de provocación oral a los alimentos es una herramienta valiosa en el diagnóstico inicial y el manejo de las reacciones adversas a los alimentos. Los síntomas sugestivos de APLV pueden ser encontrados en cerca del 5-15% de los niños. La hipersensibilidad mediada por IgE a la proteína de la LV, es predominantemente una enfermedad del período del lactante.

The incidence of food allergy (FA) in children of 2-8%. Over 90% of FA in infants are caused by cow's milk (CM), chicken egg, soy, peanuts, tree nuts, wheat, fish and seafood. There are some risk factors for the development of FA. The impact of breastfeeding on the development of allergies is controversial. There is a 0.21% of neonatal CMPA. The introduction before 4 months of life of more than 4 foods is associated with an increased risk of atopic dermatitis. The oral challenge test to food is a valuable tool in the initial diagnosis and management of adverse reactions to food. Symptoms suggestive of CMPA can be found in about 5-15% of children. The IgE-mediated hypersensitivity to the protein in the CM, is predominantly a disease of the infant period.

Alergia a la proteína de la leche de vaca: propuesta de Guía para el manejo de los niños con alergia a la proteína de la leche de vaca / Cow’s milk protein allergy: proposed guidelines for the management of children with cow’s milk protein allergy

El diagnóstico y manejo de la alergia a la proteína de leche de vaca es un verdadero desafío en la práctica pediátrica. Como se trata de una patología que pareciera estar aumentando en nuestro medio, de un modo similar a lo comunicado en otras latitudes, hemos considerado conveniente proponer una normalización de la nomenclatura y de la metodología diagnóstica. Un grupo de pediatras especialistas se ha reunido para realizar una Propuesta de Guía para el manejo de los niños con alergia a la proteína de la leche de vaca. El objetivo ha sido difundir el conocimiento actual de la fisiopatología, factores ambientales y sus manifestaciones clínicas, para colaborar con el pediatra mediante algoritmos que faciliten su manejo integral.

Cow’s milk allergy is a growing concern in the practice of pediatrics. The impression of an increasing incidence, similar to what has been reported in other latitudes, has determined the need for guidelines to help in the diagnosis and treatment of this disease. A group of pediatric specialists met to discuss the “state of the art” and propose local guidelines to deal with cow’s milk allergy. The aim has been to contribute in the understanding of the pathophysiology, environmental factors, and clinical expressions of this problem, and help pediatricians in the overall management.

Desempenho de pais de crianças em dieta de exclusão do leite de vaca na identificação de alimentos industrializados com e sem leite vaca / The performance of parents of children receiving cow's milk free diets at indentification of commercial food products with and without cows's milk

OBJETIVO: Investigar o desempenho de pais de crianças em dieta isenta da proteína do leite de vaca no reconhecimento de expressões e alimentos que contenham ou não proteínas do leite de vaca. MÉTODOS: Foram entrevistados 24 pais de crianças em dieta de exclusão do leite de vaca e derivados e 23 sem necessidade de nenhum tipo de dieta de exclusão. Foi questionado se reconheciam 12 expressões relacionadas ao leite de vaca. A seguir, foi solicitado que classificassem 10 produtos industrializados quanto ao conteúdo ou não de proteínas do leite de vaca. RESULTADOS:Termos iniciados com a palavra leite foram os mais reconhecidos pelos dois grupos. Os responsáveis por crianças em dieta de exclusão reconheceram mais freqüentemente as palavras proteína do leite de vaca, traços do leite e formulação ou preparação láctea (p < 0,05). Caseína, caseinato, lactoalbumina e lactoglobulina foram reconhecidas por menos de 25,0 por cento dos entrevistados. O número de identificação correta dos 10 produtos industrializados foi maior para os produtos com leite de vaca nos dois grupos. A mediana de acertos dos produtos com leite de vaca (n = 5) pelos pais em dieta de exclusão (4,0) foi maior que a do grupo controle (3,0; p = 0,005). Leitura de pelo menos um rótulo associou-se com maior chance de identificação correta de mais de cinco dos 10 produtos (razão de chance = 8,0). CONCLUSÃO:Apesar de orientados, os pais de crianças em dieta de exclusão não estão plenamente preparados para sua correta realização, indicando a necessidade de aprimoramento das orientações para essa dieta de exclusão.

OBJECTIVE: To investigate how well the parents of children on cow's milk free diets perform at recognizing whether or not expressions describe and foods contain cow's milk proteins. METHODS: Interviews were conducted with 24 parents of children on cow's milk and by-products exclusion diets and 23 parents of children with no need for any type of exclusion diet. They were asked if they recognized 12 expressions relating to cow's milk. They were then asked to classify 10 commercial food products in terms of whether or not they contained cow's milk proteins. RESULTS: Terms that included the word milk were more often recognized by both groups of parents. The parents of children on exclusion diets recognized the terms cow's milk protein, traces of milk and milk formulation or preparation most frequently (p < 0.05). Less than 25.0 percent of those interviewed recognized casein, caseinate, lactalbumin and lactoglobulin. Both groups correctly identified more of the commercial products containing cow's milk than those free from milk. The median number of products containing cow's milk (total = 5) correctly identified by the parents of children on exclusion diets (4.0) was greater than for the control group (3.0; p = 0.005). Reading at least one label was associated with a greater chance of correctly identifying more than five of the 10 products (odds ratio = 8.0). CONCLUSIONS: Despite having received guidance, the parents of children on exclusion diets were not fully prepared to manage these diets, indicating a need for improvements to the instruction provided when indicating exclusion diets.

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.