Plant food allergy: Influence of chemicals on plant allergens.

Plant-derived foods are the most common allergenic sources in adulthood. Owing to the rapidly increasing prevalence of plant food allergies in industrialized countries, the environmental factors are suspected to play a key role in development of allergic sensitization. The present article provides an overview of ways by which chemicals may influence the development and severity of allergic reactions to plant foods, with especial focus on plant allergens up-regulated under chemical stress. In plants, a substantial part of allergens have defense-related function and their expression is highly influenced by environmental stress and diseases. Pathogenesis-related proteins (PR) account for about 25% of plant food allergens and some are responsible for extensive cross-reactions between plant-derived foods, pollen and latex allergens. Chemicals released by anthropogenic sources such as agriculture, industrial activities and traffic-related air pollutants are potential drivers of the increasing sensitization to allergenic PRs by elevating their expression and by altering their immunogenicity through post-translational modifications. In addition, some orally-taken chemicals may act as immune adjuvants or directly trigger non-IgE mediated food allergy. Taken together, the current literature provides an overwhelming body of evidence supporting the fact that plant chemical exposure and chemicals in diet may enhance the allergenic properties of certain plant-derived foods.

Review on pathogenicity mechanism of enterotoxigenic Escherichia coli and vaccines against it.

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea in children. Colonization factors (CFs) and LT enterotoxin are the major ETEC candidate vaccines. To cause disease, ETEC must adhere to the epithelium of the small intestine by means of CFs. Watery diarrhea is produced due to the effects of the enterotoxins. Vaccine development against ETEC has been identified as an important primary prevention strategy in developing countries and for travelers to these regions. Mucosal immunization can cause secretory IgA antibody (sIgA) responses that prevents the attachment of bacteria to the intestine and are of particular importance for provide protection against ETEC infection. The design of multivalent ETEC vaccine containing various colonization factors and ETEC toxin may provide protection against a wide range of bacterial strains. In this review, the importance and pathogenesis of ETEC, and the latest ETEC vaccine research results are discussed.

Transgenic resistance.

Transgenic resistance to plant viruses is an important technology for control of plant virus infection, which has been demonstrated for many model systems, as well as for the most important plant viruses, in terms of the costs of crop losses to disease, and also for many other plant viruses infecting various fruits and vegetables. Different approaches have been used over the last 28 years to confer resistance, to ascertain whether particular genes or RNAs are more efficient at generating resistance, and to take advantage of advances in the biology of RNA interference to generate more efficient and environmentally safer, novel "resistance genes." The approaches used have been based on expression of various viral proteins (mostly capsid protein but also replicase proteins, movement proteins, and to a much lesser extent, other viral proteins), RNAs [sense RNAs (translatable or not), antisense RNAs, satellite RNAs, defective-interfering RNAs, hairpin RNAs, and artificial microRNAs], nonviral genes (nucleases, antiviral inhibitors, and plantibodies), and host-derived resistance genes (dominant resistance genes and recessive resistance genes), and various factors involved in host defense responses. This review examines the above range of approaches used, the viruses that were tested, and the host species that have been examined for resistance, in many cases describing differences in results that were obtained for various systems developed in the last 20 years. We hope this compilation of experiences will aid those who are seeking to use this technology to provide resistance in yet other crops, where nature has not provided such.

Effect of maternal intake of organically or conventionally produced feed on oral tolerance development in offspring rats.

The aim of this study was to investigate the effect of maternal consumption of organically or conventionally produced feed on immunological biomarkers and their offsprings' response to a novel dietary antigen. First-generation rats were fed plant-based diets from two different cultivation systems (organic or conventional) or a chow. Second-generation rats were exposed to ovalbumin (OVA) via their mother's milk and subsequently challenged with OVA after weaning onto the chow diet. In the chow diet group feeding the dams OVA resulted in suppression of the pups' anti-OVA antibody response to the OVA challenge (total OVA-specific IgG was 197 for the OVA-treated chow diet group and 823 for the control chow diet group (arbitrary ELISA units)). In contrast, OVA exposure of the dams from the plant-based dietary groups did not result in a similar suppression. Cultivation system had no effect on the immunological biomarkers, except for a higher spleen prostaglandin E2 (PGE2) concentration in pups originating from dams fed the conventional plant-based diet (223 ng/L) than from those fed the organic plant-based diet (189 ng/L).

In vitro modulation of oxidative burst via release of reactive oxygen species from immune cells by extracts of selected tropical medicinal herbs and food plants.

OBJECTIVE: To evaluate in vitro immunomodulating properties and potential cytotoxicity of six tropical medicinal herbs and food plants namely Antidesma madagascariense (Euphorbiaceae) (AM), Erythroxylum macrocarpum (Erythroxylaceae) (EM), Faujasiopsis flexuosa (Asteraceae) (FF), Pittosporum senacia (Pittosporaceae) (PS), Momordica charantia (Cucurbitaceae) (MC) and Ocimum tenuiflorum (Lamiaceae) (OT). METHODS: Initially, the crude water and methanol extracts were probed for their capacity to trigger immune cells' NADPH oxidase and MPO-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence, respectively; as compared to receptor-dependent (serum opsonised zymosan- OPZ) or receptor-independent phorbol myristerate acetate (PMA). RESULTS: Preliminary screening on whole human blood oxidative burst activity showed significant and concentration-dependent immunomodulating properties of three plants AM, FF and OT. Further investigations of the fractions on isolated human polymorphonuclear cells (PMNs) and mice monocytes using two different pathways for activation of phagocytic oxidative burst showed that ethyl acetate fraction was the most potent extract. None of the active samples had cell-death effects on human PMNs, under the assay conditions as determined by the trypan-blue exclusion assay. Since PMA and OPZ NADPH oxidase complex is activated via different transduction pathways, these results suggest that AM, FF and OT does not affect a specific transductional pathway, but rather directly inhibit a final common biochemical target such as the NADPH oxidase enzyme and/or scavenges ROS. CONCLUSIONS: Our findings suggest that some of these plants extracts/fractions were able to modulate significantly immune response of phagocytes and monocytes at different steps, emphasizing their potential as a source of new natural alternative immunomodulatory agents.

Pollen and plant food profilin allergens show equivalent IgE reactivity.

BACKGROUND: Profilins are commonly involved in polysensitization of allergic patients; therefore, appropriate markers should be used in component-resolved diagnosis. OBJECTIVE: To evaluate the immunological equivalence between profilins from pollens and plant-derived foods, to be used in component-resolved diagnosis. METHODS: Specific immunoglobulin (Ig) G antibodies against pollen and fruit profilins, as well as sera from patients allergic to mustard, melon, or olive pollen, were used. Purified profilins from mustard seeds, fruit melon, and chenopod and birch pollen were assayed in immunoblotting, enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition assays. RESULTS: Significant correlation was found in the response of purified profilins by ELISA and immunoblotting for both specific IgG and IgE. The highest levels of IgE binding were obtained for olive pollen-allergic patients, which could be related to the route of sensitization. The responses of individual patients to profilins were also similar and independent of the sensitizing source. The inhibition between pairs of allergens was generally higher than 70%, indicating that profilins share most of the IgE epitopes. Modeling of mimotopes in the conformational structure of the implicated profilins supports their strong cross-reactivity obtained experimentally. CONCLUSIONS: No correlation exists between the level of IgE response of individual patients to specific profilins and the corresponding theoretical sensitizing source, suggesting that the sensitization could be attributable to any profilin present in the environment of the patients. This would bear out the use of most profilins as a common marker for polysensitization in component-resolved diagnosis and for therapeutic approaches.

Does sensitization to foods in adults occur always in the gut?

It is widely accepted that, under normal conditions, the contact between allergens and the immune system via the gut results in immune tolerance. Thus, it is rather surprising that normal adults may become sensitized to foods that they have consumed a number of times without any consequence. However, the medical literature is crowded with reports suggesting that sensitization to food allergens may occur outside the intestinal tract in many instances. The present article reviews and discusses current data suggesting, either directly or indirectly, a possible initiation of food allergy in the respiratory tract or in the skin in the light of recent findings about mechanisms of tolerance and sensitization.

Cypress pollen does not cross-react to plant-derived foods.

BACKGROUND AND OBJECTIVE: Some studies hypothesize the existence of cross-reactivity between allergy to Cupressus sempervirens pollen and plant-derived foods. We aimed to assess whether this holds true. METHODS: 72 patients monosensitized to cypress pollen were investigated for food allergy to peach, apple, tomato and Juniperius oxycedrus berry. RESULTS: No patient had a history of clinical allergy or showed in-vitro or in-vitro reactivity to peach, apple, and tomato. Two patients scored positive on SPT with Juniperius oxycedrus berry but in-vitro tests ruled out cross-reactivity with the corresponding pollen. CONCLUSION: Airborne allergy to Cupressaceae pollen is not associated with allergy to plant-derived foods.

Differences among pollen-allergic patients with and without plant food allergy.

BACKGROUND: A considerable number of pollen-allergic patients develops allergy to plant foods, which has been attributed to cross-reactivity between food and pollen allergens. The aim of this study was to analyze the differences among pollen-allergic patients with and without plant food allergy. METHODS: Eight hundred and six patients were recruited from 8 different hospitals. Each clinical research group included 100 patients (50 plant food-allergic patients and 50 pollen-allergic patients). Diagnosis of pollen allergy was based on typical case history of pollen allergy and positive skin prick tests. Diagnosis of plant-food allergy was based on clear history of plant-food allergy, skin prick tests and/or plant-food challenge tests. A panel of 28 purified allergens from pollens and/or plant foods was used to quantify specific IgE (ADVIA-Centaur® platform). RESULTS: Six hundred and sixty eight patients (83%) of the 806 evaluated had pollen allergy: 396 patients with pollen allergy alone and 272 patients with associated food and pollen allergies. A comparison of both groups showed a statistically significant increase in the food and pollen allergy subgroup in frequency of: (1) asthma (47 vs. 59%; p < 0.001); (2) positive skin test results to several pollens: Plantago, Platanus, Artemisia, Betula, Parietaria and Salsola (p < 0.001); (3) sensitization to purified allergens: Pru p 3, profilin, Pla a 1 - Pla a 2, Sal k 1, PR-10 proteins and Len c 1. CONCLUSION: Results showed relevant and significant differences between both groups of pollen-allergic patients depending on whether or not they suffered from plant-derived food allergy.

Characterization of plant food allergens: an overview on physicochemical and immunological techniques.

Allergy to plant-derived foods is a highly complex disorder with clinical manifestations ranging from mild oral, gastrointestinal, and cutaneous symptoms to life-threatening systemic conditions. This heterogeneity in clinical manifestations has been attributed to different properties of allergenic molecules. Based on this fact, symptom elicitors were grouped into class I and pollinosis-associated class II food allergens, but clear distinction is rather ambiguous. Moreover, mechanisms underlying food sensitization are not fully understood yet, and food allergy management most often relies on patient's compliance to avoid suspected foods. Therefore, recent efforts aim at the investigation of plant food allergies at the molecular level. This review provides an overview on currently available techniques for allergen characterization and discusses their application for investigation of plant food allergens. Data obtained by an array of physicochemical analyses, such as allergen structure, integrity, aggregation, and stability, need to be linked to results from immunological methods at the level of IgE and T-cell reactivity. Such knowledge allows the development of computational algorithms to predict allergenicity of novel foods being introduced by biotechnological industry. Furthermore, molecular characterization is an indispensable tool for molecule-based diagnosis and future development of safer patient-tailored specific immunotherapy in plant food allergy.

Defense mechanisms against toxic phytochemicals in the diet of domestic animals.

Plant secondary metabolites (PSMs) are non-nutritional components that occur in numerous feed materials and are able to exert toxic effects in animals. The current article aims to summarize innate defense strategies developed by different animal species to avoid excessive exposure to PSMs. These mechanisms include pre-systemic degradation of PSMs by rumen microbiota, the intestinal barrier including efflux transporters of monogastric species, as well as pre-hepatic and intra-hepatic biotransformation processes. These physiological barriers determine systemic exposure and ultimately the dose-dependent adverse effects in the target animal species. Considering the large number of potentially toxic PSMs, which makes an evaluation of all individual PSMs virtually impossible, such a mechanism-oriented approach could improve the predictability of adverse effects and support the interpretation of clinical field observations. Moreover, mechanistic data related to tissue disposition and excretion pathways of PSMs for example into milk, could substantially support the assessment of the risks for consumers of foods derived from PSM-exposed animals.

Lupine, a source of new as well as hidden food allergens.

The present review summarizes current knowledge about lupine allergy, potential sensitization routes, cross-reactions between lupine and other legumes, and the respective IgE-binding proteins. Since the 1990 s, lupine flour is used as a substitute for or additive to other flours, mostly wheat flour, in several countries of the EU. In 1994, the first case of an immediate-type allergy after ingestion of lupine flour-containing pasta was reported. Since then, the number of published incidents following ingestion or inhalation of lupine flour is rising. So far, the Lupinus angustifolius beta-conglutin has been designated as the allergen Lup an 1 by the International Union of Immunological Societies Allergen Nomenclature Subcommittee. Initially, publications focussed on the fact that peanut-allergic patients were at risk to develop anaphylaxis to lupine due to cross-reactivity between peanut and lupine. At present, however, the ratio between cases of pre-existing legume allergy (mostly peanut allergy) to de novo sensitization to lupine seed is nearly 1:1. Although in December 2006, lupine and products thereof were included in the EU foodstuff allergen list according to the Commission Directive 2006/142/EC amending Annex IIIA of Directive 2000/13/EC in order to prevent severe reactions caused by "hidden food allergens", the majority of patients and medical personnel are still not aware of raw lupine seed as potentially dangerous food allergen.

[Correlation of oral allergy syndrome due to plant-derived foods with alder pollen, rbet v 1 and rbet v 2 sensitization in Yokohama region].

BACKGROUND/AIM: Oral allergy syndrome (OAS) to plant foods is often caused by cross-reactivity to pollen. We investigated whether there was any significant correlation between sensitization to the pollen of alder and Japanese cedar flying off in spring and prevalence of OAS in Yokohama region. METHODS: We measured specific IgE antibodies (CAP-FEIA: CAP) against alder and Japanese cedar in 337 outpatients with skin allergy in 2005 (M:F=167:170, 33.4 years of age, on the average). In the patients who showed positive response to CAP against alder and Japanese cedar, we also tested response to CAP against rBet v 1 and rBet v 2. In addition, we statistically analyzed whether there was any correlation between prevalence of OAS and sensitization to the pollen. RESULTS: Ratio of positive response to CAP against alder was 23.4% (79 cases) while that to CAP against Japanese cedar was 73.7% (244 cases). Response to CAP against rBet v 1 and rBet v 2 was tested in 55 cases, and the ratio of positive response to CAP against rBet v 1 was 43.6% (24 cases) while that to CAP against rBet v 2 was 27.3% (15 cases). Prevalence of OAS showed a significant positive correlation (p<0.001) with sensitization to alder, but no correlation with sensitization to Japanese cedar. CONCLUSION: It was suggested that sensitization to alder pollen would be involved in prevalence of OAS in Yokohama region.

[Oral allergy syndrome due to plant-derived foods: a clinical review of 63 patients over a period of 6 years].

BACKGROUND: The clinical features of many patients with oral allergy syndrome (OAS) due to plant-derived foods have rarely been reported in Japan. OBJECTIVES: We aimed to determine the causative foods of OAS due to plant-derived foods based on clinical features and skin prick tests (SPTs). Furthermore, we aimed to elucidate the association between causative foods and sensitized pollens in patients with OAS due to plant-derived foods. METHODS: SPTs and specific IgE measurements (CAP-FEIA: CAP) were performed in relation to foods and pollens in 118 patients with positive histories of OAS due to plant-derived foods. Patients with positive histories and with positive skin test responses were identified as having type I allergy to the causative foods. RESULTS: The mean age of 63 patients with positive histories and positive skin test responses was 29.2 years (range, 2-61 years), and there were twice as many females as male. The most frequent causative foods were found to be apple, peach, kiwi, and melon in 13, 12, 12, and 11 patients, respectively. CAP frequency was shown to be similar to that of SPT regarding apple, whereas it was less than that of SPT regarding melon, peach, and kiwi. A significant correlation between the frequencies of SPT and CAP was found regarding apple (r=0.39, p<0.05) but not peach, kiwi, and melon. Forty-one of 63 patients with OAS (66.1%) had pollinosis and/or allergic rhinitis. In patients with OAS due to apple, the positive ratio of CAP response against alder pollen was higher than that in patients with OAS due to melon. In patients with OAS due to melon, the positive ratio of CAP responses against ragweed pollen, grass pollen, and mugwort pollen was higher than that in patients with OAS due to apple. CONCLUSION: In this study, positive ratios of SPT and CAP tended to differ according to the causative food, showing a smaller potential for reaction than might be suggested by patient history. Therefore, for the time being it would be more accurate to use a skin test for the diagnosis of OAS due to plant-derived foods.

Evolutionary biology of plant food allergens.

The majority of plant food allergens can be grouped into just 4 protein families. This review summarizes the evolutionary relationships of allergenic and nonallergenic members of these families. Proteins from the prolamin superfamily have been described in vascular plants. This superfamily contains several allergenic (2S albumins, nonspecific lipid transfer proteins, and cereal amylase and protease inhibitors) and nonallergenic (hybrid proline-rich proteins, cereal indolines, and alpha-globulins) member families. The cupin superfamily comprises numerous functionally highly diverse protein families from all groups of organisms. However, allergenicity within the cupins is confined to the vicilin and legumin seed storage proteins. Profilins are ubiquitous eukaryotic proteins that are nonallergenic, with the exception of profilins from flowering plants. Finally, the Bet v 1 superfamily contains the pathogenesis-related proteins 10 family, the family of major latex proteins and ripening-related proteins, the norcoclaurine synthases, and the cytokinin-binding proteins, with pathogenesis-related proteins 10 family members from certain taxa being the only allergenic members. The study of the distribution of allergenic and nonallergenic members of protein families will provide new insights into the evolution of allergenicity and the factors that make proteins allergenic.

Detection of some safe plant-derived foods for LTP-allergic patients.

BACKGROUND: Lipid transfer protein (LTP) is a widely cross-reacting plant pan-allergen. Adverse reactions to Rosaceae, tree nuts, peanut, beer, maize, mustard, asparagus, grapes, mulberry, cabbage, dates, orange, fig, kiwi, lupine, fennel, celery, tomato, eggplant, lettuce, chestnut and pineapple have been recorded. OBJECTIVE: To detect vegetable foods to be regarded as safe for LTP-allergic patients. METHODS: Tolerance/intolerance to a large spectrum of vegetable foods other than Rosaceae, tree nuts and peanut was assessed by interview in 49 subjects monosensitized to LTP and in three distinct groups of controls monosensitized to Bet v 1 (n = 24) or Bet v 2 (n = 18), or sensitized to both LTP and birch pollen (n = 16), all with a history of vegetable food allergy. Patients and controls underwent skin prick test (SPT) with a large spectrum of vegetable foods. The absence of IgE reactivity to foods that were negative in both clinical history and SPT was confirmed by immunoblot analysis and their clinical tolerance was finally assessed by open oral challenge (50 g per food). RESULTS: All patients reported tolerance and showed negative SPT to carrot, potato, banana and melon; these foods scored positive in SPT and elicited clinical symptoms in a significant proportion of patients from all three control groups. All patients tolerated these four foods on oral challenge. Immunoblot analysis confirmed the lack of IgE reactivity to these foods by LTP-allergic patients. CONCLUSION: Carrot, potato, banana and melon seem safe for LTP-allergic patients. This finding may be helpful for a better management of allergy to LTP.

Plant foods for human health: research challenges.

Plants provide the major part of human food intake. Whilst advances in agronomic characteristics (improved yield and better pest and disease resistance) continue to be a very high priority, there is increasing opportunity to enhance the nutritional value of plant based diets by improving the nutritional quality of staple foods. We now have proof of principle that genetic engineering can be used to produce plant-derived human vaccines. In relation to plant foods for human health, the research challenges include understanding: (1) why certain foods cause adverse reactions in some individuals but not in others; (2) the mechanisms of action of apparently 'protective' foods such as fruits and vegetables. There is also a need to develop much more informative and robust methods for measuring dietary exposure to specific plant foods or food constituents, including both recent exposure, for which a metabolomics approach may be particularly helpful, and long-term exposure.

Pollen-food syndromes associated with weed pollinosis: an update from the molecular point of view.

Pollinosis patients often display adverse reactions upon the ingestion of plant-derived foods as a result of immunoglobulin E (IgE) cross-reactive structures shared by pollen and food allergen sources. The symptoms of such pollen-food syndromes (PFS) or class 2 food allergies range from local oral allergy syndrome to severe systemic anaphylaxis. Two clinical syndromes, the celery-mugwort-spice syndrome and the mugwort-mustard-allergy syndrome have been described in association with weed pollinosis. However, other associations between weed pollinosis and hypersensitivity to certain kinds of food have also been observed, like the mugwort-peach, the ragweed-melon-banana, the plantain-melon, the pellitory-pistachio, the goosefoot-fruit, the Russian thistle-saffron, and the hop-celery association. The number of allergen sources involved, the allergens, and influencing factors including geography, diet, and food preparation contribute to the high clinical complexity of PFS. So far, known causative cross-reactive allergens include profilins, lipid transfer proteins, and high-molecular weight allergens and/or glycoallergens. The current usage of nonstandardized allergen extracts poses additional problems for both diagnosis and therapy of PFS patients. Further identification and characterization of involved allergens is inescapable for better understanding of PFS and vaccine development. Panels of recombinant allergens and/or hypo-allergens are promising tools to improve both PFS diagnostics and therapy.

Plant food allergies: a suggested approach to allergen-resolved diagnosis in the clinical practice by identifying easily available sensitization markers.

BACKGROUND: Molecular biology techniques have led to the identification of a number of allergens in vegetable foods, but due to the lack of purified food proteins for routine diagnostic use, the detection of sensitizing allergens remains a nearly impossible task in most clinical settings. The allergen-resolved diagnosis of food allergy is essential because each plant-derived food may contain a number of different allergens showing different physical/chemical characteristics that strongly influence the clinical expression of allergy; moreover, many allergens may cross-react with homologue proteins present in botanically unrelated vegetable foods. OBJECTIVE: Through a review of the available literature, this study aimed to detect "markers" of sensitization to specific plant food allergens that are easily accessible in the clinical practice. RESULTS: There are several "markers" of sensitization to different allergenic proteins in vegetable foods that can be helpful in the clinical practice. Specific algorithms for patients allergic to Rosaceae and to tree nuts were built. CONCLUSION: Clinical allergologists lacking the assistance of an advanced molecular biology lab may take advantage of some specific clinical data as well as of some "markers" in the difficult task of correctly diagnosing patients with plant food allergy and to provide them the best preventive advice.