Chemical immunology and allergy最新文献

In young children, food allergy is usually acquired via the gastrointestinal tract and directed toward egg and milk. Adolescent and adult patients, however, mainly acquire food allergy via primary sensitization to inhalant allergens on the basis of cross-reactivity between proteins in inhalant sources and in food. This type of food allergy is frequently mediated by sensitization to broadly represented allergens, or so-called panallergens. Food allergic reactions in adult patients - similar to those in children - range in severity from very mild and local symptoms, as in contact urticaria of the oral mucosa, to systemic symptoms involving distal organs, to a fatal outcome. Plant foods, such as fruits, nuts, and vegetables, are the most prevalent allergenic foods in this age group.

Eosinophilic oesophagitis (EoE) is an antigen-driven pan-oesophagitis that is defined by the presence of at least 15 eosinophils per high power field on oesophageal histology in conjunction with upper gastrointestinal symptoms. EoE is closely associated with atopic disorders, in particular with food allergy, and as for other atopic diseases in childhood, there is a strong preponderance of male patients who have this disorder. The mechanisms leading to EoE have been characterised at the molecular level. Eotaxin-3, interleukin-5 and interleukin-13 are the key effector molecules in EoE pathogenesis. EoE presents with a diverse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infancy, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained as an incidental finding in patients undergoing gastroscopy for other suspected conditions, including coeliac disease. EoE is different from gastro-oesophageal reflux disease and does not improve in response to proton pump inhibitors. Therefore, EoE needs to be distinguished from so-called PPI-responsive oesophageal eosinophilia. The long-term prognosis of EoE remains poorly defined, and complications mainly relate to subepithelial remodelling and fibrosis that may result in dysmotility, dysphagia and oesophageal strictures. The treatment of EoE involves elimination diets and topical swallowed aerosolised corticosteroids, while biological therapies targeting molecular mechanisms have so far been unsuccessful. In children, elemental diets have proved highly effective, but multiple food elimination diets are more sustainable in the long term. Further randomised, controlled trials on dietary or pharmacological interventions are needed to inform the optimal long-term management of EoE.

Cow's milk allergy is among the more frequent food allergies in infants and children. Because its suspicion stems from a plethora of symptoms, it is frequently reported. However, the development of a rigorous diagnostic pathway will reduce the diagnosed children to less than 50% of those reported. Cow's milk allergy is the only specific food allergy for which an EBM guideline exists. According to the guidelines (Diagnosis and Rationale for Action against Cow's Milk Allergy), a diagnostic process based on the pre-test probability of this condition is available. Treatments include avoidance, the substitution of cow's milk with an appropriate formula, and in some cases, oral immunotherapy. Treatment choice is also guided by these guidelines.

Egg allergy is one of the most frequent food allergies in infants and young children. The prevalence of egg allergy is estimated to be between 1.8 and 2% in children younger than 5 years of age. The reactions are mainly mediated by IgE and partially by non-IgE or are a mix of both types. Egg white contains more than 20 different proteins and glycoproteins. Ovomucoid (Gal d 1), ovalbumin (Gal d 2), conalbumin (ovotransferrin) (Gal d 3) and lysozyme (Gal d 4) have been identified as major allergens in hen's egg. Alpha-livetin (Gal d 5) is thought to be a main egg yolk allergen responsible for bird-egg syndrome. The diagnosis of egg allergy is based on history taking, antigen-specific IgE measurements, such as the skin prick test, in vitro antigen-specific blood IgE tests and histamine release tests, and oral food challenges. The measurements of specific IgE to ovomucoid and its linear epitopes are more useful in the diagnosis of heated egg allergy and in the prediction of prognosis. Currently, the management of egg allergy is essentially minimal elimination based on the correct identification of the causative allergen. Although oral immunotherapy is promising as a tolerance induction protocol, several questions and concerns still remain, predominantly regarding safety.

The diagnosis of food allergy requires responses to two important questions: Does the patient have a food allergy? If so, which foods will elicit allergic symptoms? The first question will most often have to be answered following a physical examination and an interview with the patient and/or caretakers. Based on this, a provisional decision to pursue a food allergy diagnosis may be made after carefully considering other possible reasons for an adverse reaction to a food: aversion, infection, intoxication, or an underlying metabolic disease. To respond to the next question, the anamnesis is highly important in selecting which tests and, ultimately, oral food challenges the patient should undergo to reach the final diagnosis. For the diagnosing doctor, it is important to know and consider the regional pattern of inhalation and food allergies, the food consumption patterns in the local community, and the selection of patients--in terms of both age groups and symptoms--visiting the center.

Food allergy includes a number of diseases that present with adverse immunological reactions to foods and can be IgE-mediated, non-IgE-mediated, or a combination of both mechanisms. IgE-mediated food allergy involves immediate hypersensitivity through the action of mast cells, whereas non-IgE-mediated food allergy is most commonly cell-mediated. These food allergies are thought to occur as a result of a breakdown in oral tolerance and, more specifically, from an aberrant regulatory T-cell response. Ongoing studies of experimental treatments for food allergy strive to induce oral tolerance and to teach us more about the pathogenesis of food allergy.

The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome.

Food allergy is a potentially life-threatening condition affecting almost 10% of children, with an increasing incidence in the last few decades. It is defined as an immune reaction to food, and its pathogenesis may be IgE mediated, mixed IgE and non-IgE mediated, or non-IgE mediated. Potentially all foods can cause food allergy, but a minority of foods are responsible for the vast majority of reactions reported. A good clinical history is crucial for an accurate diagnosis. Allergy tests, including the skin prick test and measurement of specific IgE antibodies, are useful tools in the case of IgE-mediated or mixed allergy but have not been shown to be of any help in delayed allergic reactions to foods.

Compared with other population groups, the way of life of farmers can be viewed as being similar to that of our ancestors. The settled continuation of generations within certain critical geographical and environmental conditions requires a special local network of knowledge and experience. The immune system provides protection against microbes and their toxins. Each strong reaction impedes an active adaptation. Allergy is therefore a harmful intolerance and represents one of many different paradoxes. The aim of this chapter is to demonstrate some of the interactions of tolerance and adaptation from a historical background.

Allergic diseases are not new. They have been described in the early medical literature in various cultures like Egypt, China, indigenous America and in the Greco-Roman tradition. The terms 'idiosyncrasy', 'asthma' and 'eczema' are still in use today. The most famous allergic individual of antiquity with the whole triad of atopic diseases and a positive family history of atopy probably was Emperor Octavianus Augustus.