Alok Kumar Verma

A Comprehensive Review of Legume Allergy

Legumes belonging to Fabaceae family of the order Fabales are a rich and important source of proteins and many essential elements. Due to its nutritious elements, these are preferably included in human diet in most part of the world. But, unfortunately, IgE binding proteins have been identified in majority of legumes, and allergenic response to these legumes may range from mild skin reactions to life-threatening anaphylactic reaction. Overall, allergenicity due to consumption of legumes in decreasing order may be peanut, soybean, lentil, chickpea, pea, mung bean, and red gram. So far, several allergens from different legumes have been identified and characterized. Most of identified allergens belong to storage proteins family, profilins, or the pathogenesis-related proteins. Legumes also have property of immunological cross-reactivity among themselves and from other sources that also increases the severity of allergenic response to a particular legume. This review summarizes the currently available knowledge on legume allergy and describes the allergenic problems associated with different legumes. It also tries to explore about the legume allergens identified so far by different scientific groups. The culmination of knowledge about identification and characterization of allergens from different legumes will be helpful in diagnosis and treatment of allergy, for development of novel therapeutic strategies, for strict avoidance of particular legume in diet by susceptible individual and also to produce hypoallergenic cultivars of leguminous crop through conventional breeding or genetic modification.

Molecular mechanisms of IgE mediated food allergy

The purpose of this review is to collate current knowledge and recent advances in molecular mechanism behind the immediate type hypersensitivity of foods. Food allergy is a growing concern of human health in developed as well as developing countries now days. Food allergic reactions are mostly IgE mediated and also known as immediate type hypersensitivity or type I reaction. This review encompasses a wide range of molecular events during IgE mediated reactions like primary exposure of allergens, processing of allergens by antigen presenting cells, role of transcription factors like GATA-3, STAT-6, NF-AT, c-maf, c-kit and NF-κB, Treg cells, toll like receptors, cytokines and chemokines, class switch to IgE, FcεR1 receptor, priming of IgE on mast cells or basophils, signaling events followed by secondary exposure of allergens, degranulation and release of mediators like leukotrienes, histamines, prostaglandins, β-hexosaminidase and ultimately anaphylaxis. This review may be helpful to beginners as well as experts working in the field of allergy and immunology because of the stepwise explanations of molecular mechanisms involved in IgE mediated reactions.

Zinc oxide nanoparticles provide an adjuvant effect to ovalbumin via a Th2 response in Balb/c mice

Zinc oxide nanoparticles (ZNPs) have been used in dietary supplements and may cause an immunomodulatory effect. The present study investigated the effect of ZNPs on antigen-specific immune responses in mice sensitized with the T-cell-dependent antigen ovalbumin (OVA). BALB/c mice were intraperitoneally administered ZNPs (0.25, 0.5, 1 and 3mg) once, in combination with OVA, and the serum antibodies, splenocyte reactivity and activation of antigen-presenting cells were examined. The serum levels of OVA-specific IgG1 and IgE were found significantly enhanced by treatment with ZNPs over control. An increased level of IL-2, IL-4, IL-6, IL-17 and decreased level of IL-10 and TNF-α in splenocytes administered with ZNPs were observed in comparison with control. The ZNPs and OVA-stimulated T lymphocytes showed enhanced proliferation compared with control. Macrophages and B cells showed high expression of MHC class II, whereas higher expression of CD11b in macrophages of the ZNPs and ZNPs/OVA treated groups was observed. The lungs and spleen had increased eosinophils and mast cell numbers. Also, myeloperoxidase activity in lungs was found to be increased by 2.5-fold in the case of ZNPs and 3.75-fold increase in ZNPs/OVA, whereas in intestine, there was significant increase in both the groups. Increased expression of the genes for GATA-3, SOCS-3, TLR-4, IL-13 and IL-5 in the intestine was observed. Collectively, these data indicate that systemic exposure to a single administration of ZNPs could enhance subsequent antigen-specific immune reactions, including the serum production of antigen-specific antibodies, and the functionality of T cells.

Clinical complications of kidney bean (Phaseolus vulgaris L.) consumption.

Kidney beans (Phaseolus vulgaris L.), are common legumes, consumed worldwide. The delicacy of kidney beans is highly appreciable but, at the same time, their toxicity has raised an alarming concern. Kidney bean toxicity may be divided into two subcategories: toxicity caused by its lectins, saponins, phytates, and protease inhibitors or allergenicity induced by its allergenic proteins. The purpose of this review is to unravel the facts behind the different aspects of toxicity and allergenicity induced by kidney beans and try to fill the gaps that exist currently.

Chickpea (Cicer arietinum) proteins induce allergic responses in nasobronchial allergic patients and BALB/c mice

Allergy to chickpea or Garbanzo bean (Cicer arietinum) has been reported in the Indian population. Little information is found regarding allergenic events involved in the chickpea allergy; therefore, chickpea allergenicity assessment was undertaken. In vivo and ex vivo studies were carried out using BALB/c mice. Chickpea skin prick test positive patients have been used to extend this study in humans. Identification of allergens was carried out by simulated gastric fluids assay for pepsin resistant polypeptides and validated by IgE western blotting using chickpea sensitive humans and sensitized mice sera. Our data have shown the occurrence of a systemic anaphylactic reaction resulting in reduced body temperature after challenge along with significantly increased levels of IgE, IgG1, MMCP-1, CCL-2 as well as histamine. Further, increased Th1/Th2 (mixed) cytokine response was observed in spleen cell culture supernatants. Jejunum, lungs and spleen showed prominent histopathological changes specific for allergic inflammation. Immunoblotting with pooled sera of either sensitized mice or human sera recognized seven similar IgE binding polypeptides that may be responsible for chickpea induced hypersensitivity reactions. This study has addressed the allergenic manifestations associated with chickpea consumption and identifies the proteins responsible for allergenicity which may prove useful in diagnosis and management of allergenicity of legumes especially chickpea.

Impact of Thermal Processing on Legume Allergens

Food induced allergic manifestations are reported from several parts of the world. Food proteins exert their allergenic potential by absorption through the gastrointestinal tract and can even induce life threatening anaphylaxis reactions. Among all food allergens, legume allergens play an important role in induction of allergy because legumes are a major source of protein for vegetarians. Most of the legumes are cooked either by boiling, roasting or frying before consumption, which can be considered a form of thermal treatment. Thermal processing may also include autoclaving, microwave heating, blanching, pasteurization, canning, or steaming. Thermal processing of legumes may reduce, eliminate or enhance the allergenic potential of a respective legume. In most of the cases, minimization of allergenic potential on thermal treatment has generally been reported. Thus, thermal processing can be considered an important tool by indirectly prevent allergenicity in susceptible individuals, thereby reducing treatment costs and reducing industry/office/school absence in case of working population/school going children. The present review attempts to explore various possibilities of reducing or eliminating allergenicity of leguminous food using different methods of thermal processing. Further, this review summarizes different methods of food processing, major legumes and their predominant allergenic proteins, thermal treatment and its relation with antigenicity, effect of thermal processing on legume allergens; also suggests a path that may be taken for future research to reduce the allergenicity using conventional/nonconventional methods.

Allergenic Diversity among Plant and Animal Food Proteins

A large number of food allergens, usually proteins capable of inducing allergic symptoms, including severe, even life-threatening reactions in predisposed individuals, have been identified and characterized. As most of these proteins are from our daily dietary intake, they are often difficult to avoid. However, the proteins that cause such immunoglobulin E (IgE)-mediated reactions can be assigned to only a limited number of protein families. Detailed knowledge about the characteristics of food allergens, their structures, biological activity, and stability, may be helpful in improving diagnosis of food allergy, avoiding unnecessary exclusion of diets, and assessing the risk of cross-reactive allergies to other food sources. The purpose of this review is to shed light on the sources and molecular properties of the allergenic proteins, their stability, the mechanisms of the allergenic responses, and recent findings related to prevention of this serious issue.

Phytohemagglutinins augment red kidney bean (Phaseolus vulgaris L.) induced allergic manifestations.

UNLABELLED Red kidney bean (Phaseolus vulgaris L.), a commonly consumed bean has been reported to induce allergic reactions in susceptible individuals. Phytohemagglutinins (PHAs, mainly PHA-P) contribute a major proportion of red kidney bean seeds. However, their roles in red kidney bean induced allergic reactions are still to be explored. This study was carried out to understand the role of PHAs in allergic manifestations using BALB/c mice and cultures of splenocyte, RBL-2H3 cells as well as bone marrow mast cells (BMMCs). Also, the characterization of allergic components from PHA-P was studied by LC-MS/MS. Enhanced levels of specific IgE and IgG1, clinical scores, cytokines and chemokines, β-hexosaminidase, histamine, cysteinyl leukotriene, prostaglandin D2 and abrupt histological changes in the intestine, lung and spleen indicated a pivotal role of PHA-P in red kidney bean allergy. Further, LC-MS/MS study revealed two IgE binding components of PHA-P as PHA-L and PHA-E. Enhanced specific IgE/IgG1 and β-hexosaminidase level elucidated the possible role of PHA-L and PHA-E in allergic manifestations. Furthermore, in the presence of IgE inhibitor piceatannol, reduced β-hexosaminidase release to some extent was noticed. The up regulated expression of GATA-3 and T-bet expression was observed in PHA-L as well as PHA-E groups. Taken together, this study revealed the fact that allergenicity potential of red kidney bean may get augmented due to the presence of different phytohemagglutinins. BIOLOGICAL SIGNIFICANCE Although food allergy is an immune provocation induced mainly by dietary allergenic protein components of the food, the role of dietary lectins in the food induced allergic manifestations cannot be ruled out. Here we provide the systematic evidences about the allergenic potential of PHAs and further disclosed the culprit components as PHA-L and PHA-E. It is an important finding that the PHA-L and PHA-E can cause allergic manifestations via not only the IgE mediated pathway but also the non-IgE mediated allergic reactions as evident by the Th1/Th2 cytokines and transcription factors. Further, the PHA-L seems to be more allergenic than the PHA-E. This article is part of a Special Issue entitled: Translational plant proteomics.

A molecular insight of CTLA-4 in food allergy.

Food allergy is an immune provocation induced by certain food in susceptible individuals. Most of the food allergic manifestations are evident in the individual having impaired oral tolerance. In spite of worldwide prevalence, there is no permanent cure of food allergy. Food allergic reactions are complex immunological events that comprises of several immune molecules like IgE, IL-4, IL-13 and T-cells, therefore, researchers are trying to pick the correct molecule to find out pivotal therapeutic solutions. Being a key regulatory molecule in suppressing T-cells functional activities, cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) or cluster of differentiation-152 (CD-152) has contributed a novel and revolutionary dimension toward therapeutic research of several diseases. This review focuses on different immunological and mechanistic perspectives of CTLA-4 in correlation with food allergy.

Allergenicity potential of red kidney bean (Phaseolus vulgaris L.) proteins in orally treated BALB/c mice and passively sensitized RBL-2H3 cells

Red kidney bean (Phaseolus vulgaris L.) is one the most commonly consumed legumes that requires an in depth understanding of its allergenicity. Therefore, the aim of this study was to explore the allergenicity of red kidney bean proteins following oral exposure in BALB/c mice and elucidate the levels of Th1/Th2 transcription factors induced by red kidney bean proteins in rat basophilic leukemia cells (RBL-2H3 cells) passively sensitized with the sera of red kidney bean sensitized mice. Red kidney bean proteins showed enhanced levels of total and specific IgE, anaphylactic symptoms, thymic stromal lymphopoietin (TSLP) and peritoneal albumin over control. Enhanced release of β-hexosaminidase along with up regulated expressions of GATA-3, STAT-6, T-bet, c-MAF and NFAT were observed in the RBL-2H3 cells exposed with red kidney bean proteins when compared to that of the controls. Taken together, exposure of red kidney bean proteins may cause allergic symptoms in mice and the ambivalent effect on Th2/Th1 transcription factors in RBL-2H3 cells.