Latex-fruit syndrome

During the last decade, latex IgE-mediated allergy has been recognized as a very important medical problem. At the same time, many studies have dealt with allergic cross-reactions between aeroallergens and foods. In this context, there is clear evidence now on the existence of significant clinical association between latex and fruit allergies. Therefore, a latex-fruit syndrome has been postulated.Several studies have demonstrated that from 20% to 60% of latex-allergic patients show IgE-mediated reactions to a wide variety of foods, mainly fruits. Although implicated foods vary among the studies, banana, avocado, chestnut and kiwi are the most frequently involved. Clinical manifestations of these reactions may vary from oral allergy syndrome to severe anaphylactic reactions, which are not uncommon, thus remarking the clinical relevance of this syndrome.The diagnosis of food hypersensitivities associated to latex allergy is based on the clinical history of immediate adverse reactions, suggestive of an IgE-mediated sensitivity. Prick by prick test with the fresh foods implicated in the reactions shows an 80% concordance with the clinical diagnosis, and therefore it seems to be the best diagnostic test available nowadays in order to confirm the suspicion of latex-fruit allergy. Once the diagnosis is achieved, a diet free of the offending fruits is mandatory.Recently, some of the common allergens responsible for the cross-reactions among latex and the fruits most commonly implicated in the syndrome have been identified. Class I chitinases, with an N-terminal hevein like domain, which cross-react with the major latex allergen hevein, seem to be the panallergens responsible for the latex-fruit syndrome.     

Identification of latex UDP glucose pyrophosphorylase (Hev b UDPGP) as a novel cause of latex fruit allergy syndrome

Based on a recently published unusual ase of food allergy in a latex-allergic patients, the present study identifies Hev b UDPGP as a novel allergen in natural rubber latex able to cause latex-fruit allergy syndrome and as a novel, potential pan-allergen in vegetable foods.     

Latex allergy in children.

Allergic or immediate hypersensitivity reactions to natural rubber latex have been reported in children with increasing frequency in the last few years, although severe anaphylactic reactions are rare. Indubitably rubber has been employed in thousands and thousands of everyday products for over a century, yet only recently has natural rubber latex allergy been recognized as a substantial medical problem. Children with spina bifida undergoing multiple surgical procedures, as well healthy babies appear at high risk for natural rubber latex allergy, with life-threatening reactions reported during surgery or while playing with balloons. Skin prick testing is the preferred diagnostic method, especially in the prick by prick version. Parents of children with latex allergy should take caution that their babies avoid contact with rubber products, and that a latex-free environment is set during procedures. Since even minimal contact with natural rubber latex products may produce reactions, the primary treatment for latex allergy is avoidance. In this paper we review the new natural rubber latex allergens, as well as the cross-reactions regarding the latex-fruit syndrome since the recent characterization of a number of profilins has also greatly widened the number of possible reactions.     

Components of plant-derived food allergens: Structure,diagnostics, and immunotherapy

A large number of plant-derived food allergen components have been identified to date. Although these allergens are diverse, they often share common structural features such as numerous disulfide bonds or oligomeric structures. Furthermore, some plant-derived food allergen components cross-react with pollen allergens. Since the relationship between allergen components and clinical symptoms has been well characterized, measurements of specific IgE to these components have become useful for the accurate clinical diagnosis and selection of optimal treatment methods for various allergy-related conditions including allergy caused by plant-derived foods. Herein, I have described the types and structures of different plant allergen components and outlined the diagnosis as well as treatment strategies, including those reported recently, for such substances. Furthermore, I have also highlighted the contribution of allergen components to this field.     

IGE-mediated natural rubber latex allergy: an update

In the past 2 decades, IgE-mediated NRL allergy has become a well-defined condition with recognised risk groups, established diagnostic tools, and adequate prevention strategies (1-3). Furthermore, molecular biology and biochemical techniques have significantly improved our knowledge of the proteins responsible to cause the disease. Clinical manifestations will not be addressed in this review, nor will broad preventive strategies be proposed; these have been discussed elsewhere (4, 5). After a brief introduction this review will focus on specific issues: (1) How do we estimate the prevalence of NRL allergy and who is at risk for clinical sensitisation? (2) What specific allergens cause NRL allergy? How does sensitisation for these allergens occur? Are all patients sensitised for the same allergens? Threshold allergen exposure levels. (4) What is the latex-fruit syndrome? What is the clinical relevance of a positive plant food specific IgE quantification in patients with NRL allergy? (5) How do we diagnose NRL allergy? What are the strengths and weaknesses of currently available diagnostic tools? (7) How do we manage NRL allergy? What is the role of medication and immunotherapy in the treatment of NRL allergy? How do we select an appropriate non-NRL alternative for NRL gloves? Which regulatory provisions have been implemented?     

New insights in allergen avoidance measures for mite and pet sensitized patients. A critical appraisal

It is widely acknowledged that avoidance of allergens such as those derived from foods, drugs, latex and stinging insects results in a complete disappearance of symptoms. By contrast, although it has been clearly shown that allergens are an important risk factor for the development of respiratory symptoms and that several avoidance measures reduce allergen levels, whether this gives clinical improvement in symptoms is debatable. Many reasons could be invoked to justify this evident discrepancy. Apart from the intrinsic methodological aspects (e.g. single or combined interventions measure, population studied, severity of respiratory symptoms, outcomes, evaluated parameters, etc.), it is important to outline that a successful approach requires that the avoided allergen is the only and real factor responsible for symptoms, the patient's education and the use of a comprehensive protocol to reduce allergen exposure. Other important factors include the involvement of the patient, the relevance of other allergens/non-specific agents, and exposure to sensitizing agents also outside patient's home. It is likely that the clinical phase of allergic airway disease and the degree of bronchial (and also nasal) remodelling, in each individual, represent relevant factors for the clinical outcome of allergen avoidance procedures. Since the management of respiratory allergy is a complex strategy (including drugs, allergen avoidance, immunological and educational interventions), it is difficult in real life to distinguish the efficacy of a single intervention in comparison to the others. A combined strategy is likely to produce better clinical results.     

Latex-vegetable syndrome due to custard apple and aubergine: new variations of the hevein symphony.

An increasing number of vegetables with crossreactions to latex are being described in patients with latex-vegetable syndrome. We present two of these vegetables, custard apple linked in two previous cases with latex sensitisation, and aubergine, that had not been described up to now in patients with latex sensitisation. The diagnosis of both cases was based on the clinical history, positive skin prick test (SPT) and specific IgE to the offending vegetables, as well as to positive SPT and specific IgE levels to latex and the major fruits involved in the latex-fruit syndrome (avocado, banana, and chestnut). Further, crude extracts from latex, custard apple and aubergine, as well as the purified allergens Hev b 6.02 and Prs a 1 were used in in vitro and in vivo assays: IgE immunodetection, histamine release (HRT) and basophil activation (BAT) tests and skin prick tests. In case 1, both purified Hev b 6.02 and Prs a 1 induced positive responses in skin prick tests, high levels of basophil activation and histamine release. Specific IgE immunodetection uncovered a reactive band of 45 kd in the crude custard apple extract, which was also recognized by anti-chitinase monospecific antibodies. The serum from patient 1 also detected Prs a 1 in immunodetection. Hev b 6.02 produced positive skin responses and showed high biological activity in HRT and BAT in the case of patient 2. However, Prs a 1 was reactive neither in SPT nor in IgE immunodetection. In fact, no band was detected using the serum of patient 2 in avocado or aubergine extracts. By contrast, Prs a 1 reached high values of basophil activation and over 10% of histamine release in case 2.     

Allergy to cassava: a new allergenic food with cross-reactivity to latex.

Patients who are allergic to latex (Hevea brasiliensis) may exhibit cross-hypersensitivity with foods. We present a case of anaphylaxis due to cassava in a patient suffering from pollinosis, latex allergy, and latex-fruit syndrome. We performed sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with cassava, avocado, chestnut, banana, kiwi, and latex extracts in order to analyze the protein bands and their molecular weights, and identify immunoglobulin (Ig) E-binding bands. Immunoblot inhibition and enzyme-linked immunosorbent assay (ELISA) inhibition were performed with latex in order to assess cross-reactivity. Cassava exhibited numerous protein bands, 5 of which were IgE-binding (89.75, 46.28, 26.68, 21.38, and 19.49 kd). These cassava IgE-binding bands were 100% inhibited by preincubation of the patient's serum with latex extract. The ELISA inhibition between latex and cassava was 23%. Our results confirm cassava as another food with clinical cross-reactivity in patients suffering from latex allergy.     

Latex allergy and fruit cross-reaction in subjects who are nonatopic.

Since the first case reported in 1927, latex allergy has attracted the attention of allergists including its capacity to cross-react with fruits. To evaluate the frequency of sensitivity to some fruit allergens shown to cross-react with latex, we evaluated 82 patients (43 men and 39 women, aged between 18 and 45 years) with latex allergy. All patients underwent skin tests with various fruit extracts that potentially cross-react with latex. Only patients with negative prick tests successively underwent prick-by-prick tests with fresh fruits. Thirty-nine of 82 patients (47.5%) were found to have positive skin tests. Prick tests with fruit extracts were positive in 28 patients (kiwi, 21 patients; banana, 17 patients; avocado, 8 patients; and papaya, 3 patients), and the prick-by-prick test had positive results in 11 patients (kiwi, 7 patients; banana, 4 patients; and avocado, 3 patients). In our experience patients with latex allergy are at a high risk of sensitization to some fruits and they often develop allergic reactions, even severe ones, after eating them; for this reason fruit sensitization should be taken into consideration when investigating patients allergic to natural rubber latex.     

Sensitivity and specificity of food specific IgE and IgG determinations for the diagnosis of food allergy

Among the methods currently used to demonstrate a sensitization to foods, the measurement of food specific IgE antibodies (sIgE) is the most practical but not the most accurate. The "sensitivity" of food sIgE determinations is, for example, suboptimal with unstable allergens in fruits and vegetables that are involved in the (birch) pollen-related immediate oral allergy syndromes. In this particular syndrome the history is often conclusive and can be substantiated by skin prick tests with fresh foods. The "sensitivity" of sIgE tests is much better when sIgE are directed to stable plant or animal food allergens which often cause non-immediate generalized reactions. Foods, usually, contain many different (glyco)proteinic allergens of which some are stable and others not. The "sensitivity" of the sIgE test with a particular food, therefore, varies according to the type of allergen that is recognized by the patient. The "specificity" of sIgE tests with foods is affected by the existence of homologous food allergens which induce cross-reactive IgE that may or may not be clinically relevant. While variable, clinical cross-reactivity is more common among botanically-related fruits, among different nuts, among mammalian foods and among seafood than among cereals, grains and legumes. The "specificity" of food sIgE tests is much better when sIgE are directed to unique non-cross-reactive food allergens. Unfortunately, neither the presence of food sIgE nor its level are predictive of clinical reactivity. The identification of individual allergens in foods and the characterization of the relevant IgE binding sites in these allergens might lead to the development of tests that only measure sIgE to clinical relevant food allergens.     

Differential expression of allergens on the internal and external surfaces of latex surgical gloves

BackgroundDifferences in latex allergen sensitization profiles have been described between children undergoing repeated surgical interventions and health care workers. The purpose of this study was to determine whether such sensitization profiles are associated with differences in the expression of latex allergen between the internal and external surfaces of surgical gloves.MethodsExtracts were obtained from whole surgical gloves as well as from their external and internal surfaces. The extracts were centrifuged, filtered, concentrated, dialyzed and lyophilized. The protein profile of the extracts was analyzed using hydrophobic interaction chromatography (HIC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting was performed using era from two patients with confirmed latex allergy. Latex recombinant allergen-specific IgE in these two patients was determined using a fluorescence enzyme immunoassay (FEIA) method. Latex allergen quantification was determined on both glove surfaces using an ELISA method.ResultsHIC and SDS-PAGE showed qualitative and quantitative differences in proteins between the internal and external glove surfaces, with the former being much richer in proteins. Immunoblotting of glove extracts using sera from two latex-allergic health workers showed differences between glove surface extracts. ELISA quantification of latex allergens demonstrated that the internal glove surface had high amounts of Hev b 5 and Hev b 6.02 whereas the external surface showed Hev b 1, Hev b 3, and Hev b 6.02.ConclusionsOur results reveal substantial differences in the composition of latex allergen profiles between the internal and external surfaces of surgical latex gloves, which may suggest a relationship between latex allergen localization and sensitization routes in different risk groups.     

Avoidance of allergens as an environmental method in the prevention of inhaled allergy symptoms

Asthma and other inhaled allergies are some of the most common paediatric diseases. The association of exposure to allergens with induction and exacerbation of symptoms has been proven. The majority of allergens are permanently or periodically suspended in the air, which leads to impaired quality of life for sensitive patients. Therefore, many methods of prevention and therapy of allergic diseases have been developed. The method of allergen exposure avoidance is often the first and the most significant measure. The present research has been conducted to evaluate, based on scientific data, which measures have the most reliable evidence of effectiveness. Environmental allergen avoidance methods, despite limited evidence supporting their clinical efficacy, are listed as the main therapeutic approaches in most recommendations. The significance of the holistic approach is also emphasised: only simultaneous introduction of several avoidance methods can bring possibly beneficial effects for the patient.     

Addressing Molecular Diagnosis of Occupational Allergies

Purpose of Review

Numerous clinically relevant allergenic molecules enhance the performance of specific (s) IgE tests and improve the specificity of allergy diagnosis. This review aimed to summarize our current knowledge of the high-molecular-weight allergens involved in the development of occupational asthma and rhinitis and to critically analyze the contribution of component-resolved diagnosis in the management of these conditions.

Recent Findings

There is a lack of standardization and validation for most available extracts of occupational agents, and assessment of sIgE reactivity to occupational allergen components has been poorly investigated, with the notable exception of natural rubber latex (NRL) and wheat flour. In the case of NRL, the application of recombinant single allergens and amplification of natural extracts with stable recombinant allergens improved the test sensitivity. IgE-sensitization profile in patients with baker’s asthma showed great interindividual variation, and extract-based diagnostic is still recommended. For other occupational allergens, it remains necessary to evaluate the relevance of single allergen molecules for the sensitization induced by occupational exposure.

Summary

Progress has been made to characterize occupational allergens especially NRL and wheat, although there is still an unmet need to increase the knowledge of occupational allergens, to include standardized tools into routine diagnostic, and to evaluate their usefulness in clinical practice.

     

Intraoperative anaphylactic shock in a child with no history of type I hypersensitivity

Natural rubber latex is the second most implicated agent in intraoperative anaphylactic reactions. This report describes a case of intraoperative anaphylaxis occurring in a non-atopic fourteen-year-old girl undergoing multiple surgical procedures, but without spina bifida, in which latex surgical gloves were the main culprit for the anaphylactic reactions. Clinical manifestations of an anaphylactic reaction were also experienced during the examination of the possible cause of intraoperative anaphylaxis by skin prick testing with a latex allergen extract. Skin tests with anesthetics were negative. Specific IgE to latex was positive at 92.9 kUA/L (class 5). The molecular basis for the reported intraoperative anaphylaxis was ascribed to three low-molecular mass latex allergens (10-15 kD) detected in the brand of latex surgical gloves used during the operation. Given the potential of a dramatic outcome, latex allergy testing as a regular preoperative measure may contribute to the reduction of anaphylactic reactions during surgical interventions.     

Elimination of airborne allergens from the household environment

Exposure to allergens could be either a risk factor of sensitization and nonspecific hyperresponsiveness in genetically predisposed patients or a risk of onset of asthma attack in certain allergic asthma. During the past 20 years, in western countries the houses have become higher and the number of furred pets have increased and have been more kept inside the house which makes probable that exposure to indoor aeroallergen has increased. The development of new methods of allergen measurements allows a more precise identification of allergen source and reservoirs, an assessment of allergen exposure and a monitoring of allergen eviction methods. Concerning mite allergens, controlled studies which showed a clinical efficacy are those with a global mite eviction and at least a 6 months follow-up for cat and dog allergens, high efficiency-filters air cleaners or vacuum-cleaners are able to reduce airborne cat or dog allergen levels. According to the increasing number of papers about allergen eviction, it seems logical to propose allergen eviction as "first line treatment" of allergic asthma. In the future, it would be interesting to develop biological markers to identify more accurately patients who have a clinical improvement after allergen eviction.     

Les allergènes recombinants : leur apport à l’allergologie en 2006

Advances in molecular biology techniques have led to the production of recombinant allergens, about thirty of them now being available for measurements (DIAGNOSIS?) in vitro. These recombinant allergens correspond to a precise molecular variant of a natural allergen, and their biological activity has to be evaluated in comparison with the corresponding natural allergen. The advantages of recombinant allergens are essentially the creation of allergenic preparations having constant pharmaceutic properties, which allows determination of specific IgE directed against different molecular components of an allergenic source, for example, pollen, mites, etc. The main consequences of these biological advances are the following: evaluation of sensitivities to allergen molecules in different populations (molecular epidemiology), improvement of extracts used for diagnosis by selection of the most pertinent allergenic sources and in quantifying their major allergen content, definition of the spectrum of recognition of specific IgE vis-à-vis different molecular components (spectrotype), quantitative evaluation of IgE responses, establishing the molecular basis of cross-reactions between different inhaled allergens, between different food allergens, and between inhaled allergens and food allergens. As regards allergy practice, this new diagnostic tool can lead to better interpretation of polysensitivities, observed by skin tests and in vitro tests. Some examples of particular clinical cases associated with specific sensitivities vis-à-vis certain recombinant allergens will be presented.     

What makes a food protein an allergen?

Food allergens are almost always proteins, but not all food proteins are allergens. This one statement sums up the purpose of this article, defining the difference between an innocuous food protein and a food allergen. The simplest answer is that a food allergen has the ability to first elicit an IgE response, and then, on subsequent exposures, to elicit a clinical response to the same or similar protein. However, this simplistic answer avoids the more complex issues of defining the biochemical characteristics that allow a food protein to survive the extremes of food processing, escape the digestive enzymes of the human gastrointestinal tract, and interact with the immune system. More than 700 allergen sequences have been identified from food and nonfood sources. However, despite increasing knowledge of the structure and amino acid sequences of the identified allergens, only a few biochemical characteristics can be associated with food allergens. Food allergen characteristics, including abundance of the protein in the food; multiple, linear IgE binding epitopes; resistance of the protein to digestion and processing; and allergen structure are discussed, and the possible reasons they predispose some food proteins to become allergens are suggested.     

Allergen immunotherapy - a position paper of the German society for allergology and clinical immunology

Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.     

A new quantitative in vitro for the detection of latex-specific IgE antibodies

Immediate-type hypersensitivity to latex allergens has resulted in anaphylactic shock and death in numerous reported cases. The allergenic proteins of latex are contained within the natural rubber extract of Hevea brasiliensis and are eluted into the final product during the manufacturing process. The quantity and types of latex allergens found in different latex products depends on the manufacturing process. Not all of these allergens are available for use in the latex prick skin test, and as a result, such tests may not be conclusive. Furthermore, application of such allergens to the skin of undiagnosed hypersensitive individuals may have harmful effects on their health. Therefore, it is important to be able to utilize in vitro methods, which reliably identify latex allergy without placing hypersensitive individuals at risk. We have developed a relatively simple and new enzyme immuno-assay (EIA) method for the detection of latex allergy. This in vitro method is quantitative and allows for the classification of allergy to latex in a short time. In comparative studies, ninety-nine serum specimens with documented clinical history of latex allergy were tested by this method, and the results paralleled those of the skin prick test performed by an independent group. The data showed that the specificity and sensitivity of our assay approaches 97.5% and 100%, respectively. We conclude that, by using a simple assay, the detection of specific IgE to latex proteins may be valuable for screening individuals and for the diagnosis of allergy to latex.     

Genetically engineered vaccines

The application of recombinant DNA technology to allergen research has provided the sequence information and genetic material to produce new types of allergy vaccines. One general strategy has been to use the knowledge to produce synthetic peptides that represent selected T-cell or B-cell epitopes. The production of genetically engineered allergens provides an alternative strategy to construct hypoallergenic vaccines, which can provide a better and less selected representation of the epitopes. Many strategies have been used to produce such hypoallergens, and their ability to reduce allergenicity has been amply demonstrated by skin and nasal provocation tests. The retention of T cell-stimulating activity has also been demonstrated, and a consistent feature of the vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity, the ability to induce anti-allergen IgG antibody. The lead hypoallergens have been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1. A clinical trial with these medicaments has shown the ability to modify IgE and IgG antibody production, skin test reactivity, and symptom scores. This is the first trial of a recombinant allergy vaccine, and it has set a benchmark for further studies. A new generation of hypoallergens is now being produced based on the detailed knowledge of the tertiary structures of the allergens and of the T-cell and B-cell epitopes. The modifications have been made to change the topography of the allergens while retaining a stable, folding structure. In the case of Bet v 1, tertiary structures of hypoallergens have been determined. Structurally modeled hypoallergens have been produced for pollen, venom, food, and latex allergens, with promising characteristics from preclinical studies.