Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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Although immediate-Type I skin reactions to human dander have been described six decades ago, only the recent application of molecular biology to allergology research allowed fast and detailed characterization of IgE-binding autoantigens. These can be functionally subdivided into three classes: (1) self-antigens with sequence homology to environmental allergens belonging to the class of phylogenetically conserved proteins, (2) self-antigens without sequence homology to known environmental allergens, and (3) chemically modified self-antigens deriving from workplace exposure. As environmental allergens, also IgE-binding autoantigens belong to different protein families without common structural features that would explain their IgE-binding capability. ⋯ Well documented is their ability to induce immediate Type I skin reactions in vivo, and to induce mediator release from effector cells of sensitized individuals in vitro. Based on these observations it is reasonable to assume that IgE-mediated cross-linking of FcRIε receptors on effector cells can elicit the same symptoms as those induced by environmental allergens, and this could explain exacerbations of chronic allergic diseases in the absence of external exposure. However, because most of the described IgE-binding self-antigens are intracellular proteins normally not accessible for antigen-antibody interactions, local release of the antigens is required to explain the induction of symptoms.
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Food allergy is a growing clinical and public health problem world-wide. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, but it is yet to be determined whether environmental factors might act in interaction with genetic risk. ⋯ The consideration of the role of epigenetics in food allergy is likely to provide an insight into aetiological and biological disease mechanisms. This paper discusses the current state of knowledge regarding genetic and environmental risk factors for food allergy, and considers the potential for furthering our understanding of food allergy aetiology by examining the role of epigenetic variation.
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Cyclodextrins, oligosaccharides linked in a circular arrangement around a central cavity, are used extensively in the pharmaceutical industry to improve drug delivery. Their usefulness depends on their capacity to form a drug inclusion, or host-guest, complex within the cavity. In an attempt to improve the delivery of the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium inclusion complex was formed with a chemically modified γ-cyclodextrin. ⋯ Important questions related to antibody accessibility of drug allergenic structures on the rocuronium-sugammadex inclusion complex, and the competition between sugammadex and IgE antibodies (both free and cell bound) for rocuronium, also remain and can be investigated in vitro. The sugammadex findings indicate that the use of carrier molecules such as the cyclodextrins to improve drug delivery will sometimes give rise to changed immunologic and allergenic behaviour of some drugs and this will have to be taken into account in preclinical drug safety assessments of drug-carrier complexes. The possibility of encapsulating and removing other allergenic drugs, e.g., penicillins and cephalosporins, in cases of difficult-to-reverse anaphylaxis to these drugs is discussed.
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Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB(4) , are potent lipid mediators that have a role in the pathophysiology of asthma. At least two receptor subtypes for CysLTs, CysLT(1) and CysLT(2) , have been identified. The activation of the CysLT(1) receptor is responsible for most of the pathophysiological effects of CysLTs in asthma, including increased airway smooth muscle activity, microvascular permeability, and airway mucus secretion. ⋯ The identification of subgroups of asthmatic patients who respond to CysLT(1) receptor antagonists is relevant for asthma management as the response to these drugs is variable. CysLT(1) receptor antagonists have a potential anti-remodelling effect that might be important for preventing or reversing airway structural changes in patients with asthma. This review discusses the role of LTs in asthma and the role of LT modifiers in asthma treatment.
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It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). ⋯ If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.