Rinkesh Kumar Gupta

Maillard reaction in food allergy: Pros and cons

ABSTRACT Food allergens have a notable potential to induce various health concerns in susceptible individuals. The majority of allergenic foods are usually subjected to thermal processing prior to their consumption. However, during thermal processing and long storage of foods, Maillard reaction (MR) often takes place. The MR is a non-enzymatic glycation reaction between the carbonyl group of reducing sugars and compounds having free amino groups. MR may sometimes be beneficial by damaging epitope of allergens and reducing allergenic potential, while exacerbation in allergic reactions may also occur due to changes in the motifs of epitopes or neoallergen generation. Apart from these modulations, non-enzymatic glycation can also modify the food protein(s) with various type of advance glycation end products (AGEs) such as Nϵ-(carboxymethyl-)lysine (CML), pentosidine, pyrraline, and methylglyoxal-H1 derived from MR. These Maillard products may act as immunogen by inducing the activation and proliferation of various immune cells. Literature is available to understand pathogenesis of glycation in the context of various diseases but there is hardly any review that can provide a thorough insight on the impact of glycation in food allergy. Therefore, present review explores the pathogenesis with special reference to food allergy caused by non-enzymatic glycation as well as AGEs.

Health Risks and Benefits of Chickpea (Cicer arietinum) Consumption

Chickpeas (CPs) are one of the most commonly consumed legumes, especially in the Mediterranean area as well as in the Western world. Being one of the most nutritional elements of the human diet, CP toxicity and allergy have raised health concerns. CPs may contain various antinutritional compounds, including protease inhibitors, phytic acid, lectins, oligosaccharides, and some phenolic compounds that may impair the utilization of the nutrients by people. Also, high consumption rates of CPs have enhanced the allergic problems in sensitive individuals as they contain many allergens. On the other hand, beneficial health aspects of CP consumption have received attention from researchers recently. Phytic acid, lectins, sterols, saponins, dietary fibers, resistant starch, oligosaccharides, unsaturated fatty acids, amylase inhibitors, and certain bioactive compounds such as carotenoids and isoflavones have shown the capability of lowering the clinical complications associated with various human diseases. The aim of this paper is to unravel the health risks as well as health-promoting aspects of CP consumption and to try to fill the gaps that currently exist. The present review also focuses on various prevention strategies to avoid health risks of CP consumption using simple but promising ways.

Pathophysiology of IL-33 and IL-17 in allergic disorders

Allergic diseases are among common clinical conditions, affecting millions of children and adults throughout the world. Food allergies, skin allergies (atopic dermatitis), and respiratory allergies (allergic rhinitis and asthma) are the common types of allergies. Recently discovered cytokines IL-17 and IL-33 have been found to play an important role in the pathogenicity of various hypersensitive disorders. After exposure to allergens or infection with parasites or viruses, IL-17 and IL-33 producing cells, such as Th17 and specialized epithelial cells respectively, become activated and trigger the pathogenic immune responses in different susceptible conditions. Potent inhibitors of these cytokines have been identified recently that may represent potential therapeutic agents to overcome the clinical complications of allergies. In the present review, we have discussed the cellular sources, modes of action and regulation of IL-17 and IL-33 in the context of hypersensitive diseases. We have also assessed the therapeutic potential of inhibitory molecules that may alter production of both these cytokines, and thus modulate susceptible conditions.

Elucidation of immediate type I reactions in native and GM mustard (Brassica spp.)

Mustard, a widely consumed spice can provoke allergic manifestations in mustard sensitive individuals. The aim of this study is to explore the allergenicity potential of GM mustard varieties (GM-V2 and GM-V4) having increased carotenoid content and compare it with the native (Varuna) and commercially available variety (Urvashi). Mustard protein sensitized (GM and non-GM) BALB/c mice sera were used to identify the allergenic proteins by IgE immunoblotting. Immunoglobulin levels, mouse mast cell protease-1, monocyte chemotactic protein and histamine were measured in serum. The levels of Th1/Th2 transcription factors GATA-3, T-bet, SOCS3, STAT 6 and c-maf in intestinal proteins of all groups were detected by immunoblotting and PCR. Major IgE-binding proteins of 21, 29 and 33kDa were found in all mustard varieties. The enhanced levels of Th2 cytokines IL-4, IL-5 and IL-13 and transcription factors GATA-3 and SOCS-3 were observed. The increased levels of MCP-1, MCPT-1 and histamine were also evident in commercial, native, GM-V2 and GM-V4 varieties of mustard treated groups. Conclusively, all these finding indicate that introduction of GM mustard varieties with increased carotenoid content did not cause any increase in allergenicity as compared to its native counterpart and therefore can be safe from allergenicity point of view.

Allergic manifestation by black gram (Vigna mungo) proteins in allergic patients, BALB/c mice and RBL-2H3 cells

The prevalence of black gram (Vigna mungo) induced allergic reactions are reported from several parts of the world including Asia and Australia. But, a thorough exploration of the allergic reactions induced by black gram proteins is still lacking. Therefore, efforts have been made to explore black gram allergy using in vivo and in vitro approaches. In this study, Simulated Gastric Fluid (SGF) assay and IgE immunoblotting were carried out to identify clinically relevant allergens of black gram. BALB/c mice and RBL-2H3 cells were used for elucidation of allergenic reactions of black gram proteins. Further, this study was extended to screen black gram sensitive patients among nasobronchial allergic patients on the basis of clinical history, skin prick test (SPT), specific IgE levels and IgE immunoblotting. Enhanced levels of specific IgE, IgG1/IgG2a (p < 0.05), histamine (p < 0.05), clinical symptoms, pathological indications in the lungs, intestine and spleen were evident in black gram sensitized BALB/c mice. Moreover, the expression of Th2 cytokine transcripts and GATA-3/T-bet ratio was found enhanced in the treated group. In vitro studies on RBL-2H3 cells,showed increased release of β-hexosaminidase (p < 0.05), histamine (p < 0.05), cysteinyl leukotriene (p<0.05) and prostaglandin D2 (p < 0.05). Further, 8.5% of screened patients were found allergic to black gram and concomitant sensitization with other allergens has shown the possibility of further enhancement in allergenic problem. Conclusively, the present study suggested that black gram consumption may be responsible for inducing immediate type of allergic sensitization in susceptible subjects.

Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote TH2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice

Abstract Epicutaneous (EC) sensitization to food allergens may occur when the skin has been lightly damaged. The study here tested whether cutaneous exposure to pigeon pea protein(s) may cause allergic sensitization. BALB/c mice were either orally gavaged or epicutaneously sensitized by repeated application of pigeon pea crude protein extract (CPE) on undamaged areas of skin without any adjuvant; afterwards, both groups were orally challenged with the pigeon pea CPE. Anaphylactic symptoms along with measures of body temperature, MCPT-1, TSLP, pigeon pea-specific IgE and IgG1, myeloperoxidase (MPO) activity, TH2 cytokines, TH2 transcription factors (TFs) and filaggrin expression were determined. Mast cell staining, eosinophil levels and histopathological analysis of the skin and intestines were also performed. In the epicutaneously-sensitized mice, elevated levels of specific IgE and IgG1, as well as of MCPT-1, TSLP, TH2 cytokines and TFs, higher anaphylactic scores and histological changes in the skin and intestine were indicative of sensitization ability via both routes in the pigeon pea CPE-treated hosts. Elevated levels of mast cells were observed in both the skin and intestine; increased levels of eosinophils and MPO activity were noted only in the skin. Decreased levels of filaggrin in skin may have played a key role in the skin barrier dysfunction, increasing the chances of sensitization. Therefore, the experimental data support the hypothesis that in addition to oral exposure, skin exposure to food allergens can promote TH2-dependent sensitization, IgE-mediated anaphylaxis and intestinal changes after oral challenge. Based on this, an avoidance of cutaneous exposures to allergens might prevent development of food anaphylaxis.

Simple Extraction Cum RP-HPLC Method for Estimation of Nanotized Quercetin in Serum and Tissues of Mice

In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer activities of quercetin (3,3′,4′,5, -pentahydroxyflavone). The nanotization of quercetin was shown to enhance its therapeutic efficacy due to smaller particle size. In the present study, an additional step was added to simple extraction cum RP-HPLC method for the quantification of nanotized quercetin (nQ) in biological samples to understand the pharmacokinetics and biodistribution of nQ following intravenous administration. The proposed method involves extraction of nQ from blood serum and tissues of mice with 2N HCl in comparison to well-known DMSO:MeOH mix method. The HCl extraction was found to be 2 – 3 times more efficient than DMSO:MeOH mix method. Results showed that the amount of nQ at various time intervals in the serum and tissues was 2 – 3 fold greater for HCl extraction than for DMSO:MeOH mix method, suggesting that HCl extraction must take into account nQ bound with protein. The reversed-phase HPLC was used for nQ detection, which showed the nQ retention time of 3.2 min. The limit of detection of nQ in blood serum was found to be 0.1 μg/mL. The proposed method was also validated in terms of linearity, precision, and accuracy.

Allergenicity assessment of Buchanania lanzan protein extract in Balb/c mice

&NA; Tree nuts are among “Big Eight” and have been reported globally for causing allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian population. However, very little is known about B. lanzans induced allergic manifestation. Therefore, evaluation of its allergenic potential was undertaken. Bl‐crude protein extract sensitized BALB/c mice sera were used to identify the allergic proteins by its IgE binding capability. The major IgE binding proteins found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa. Specific IgE, specific IgG1, MCPT‐1, PGD2 and histamine were assessed in mice sera. Enormous amount of mast cell infiltration was noted in different organs. The levels of Th1/Th2 transcription factors GATA‐3, SOCS3 and STAT‐6 were found upregulated, whereas T‐bet was downregulated. Furthermore, elevated Th1/Th2 cytokine responses were observed in mice sera. All together, these reactions developed systemic anaphylaxis upon Bl‐CPE challenge in sensitized BALB/c mice. In order to confirm the evidences obtained from the studies carried out in BALB/c, the investigation was extended to human subjects as well. Control subjects and allergic patients were subjected to skin prick test (SPT). Later sera collected from those positive to SPT along with controls were used for IgE immunoblotting. The study evaluated the allergic manifestation associated with Bl, and identified its proteins attributing Bl‐mediated allergy. This work may help in managing tree nuts mediated allergies especially due to Buchanania lanzan sensitization. Graphical abstract Figure. No caption available. HighlightsPrevalence of Bl mediated allergy is increasing due to its excessive usage in food preparations.Bl‐CPE consists of seven IgE binding proteins with M.W. of 11, 20, 23, 25, 48, 54 and 65 kDa.Bl induced the expression of allergic parameters like IgE, IgG1, TSLP, MCPT‐1, Histamine, PGD2 and CysL.Bl elicits T cells and B cells activation along with the plethora of TH2 cytokines (IL‐4, IL‐5, and IL‐13).Bl shows cross‐reactivity among the tree nuts (cashew, pistachio and peanut).

A Comprehensive Review on Mustard-Induced Allergy and Implications for Human Health

Mustard is widely used in a variety of foods/food products to enhance the flavor and nutritional value that subsequently raise the risk of hypersensitivity reactions. Mustard allergy has been reported for many years and is increasing gradually especially in the areas where its consumption is comparatively higher, and it may be considered among the most important food allergies. A number of relevant clinical studies focused on mustard-induced allergic manifestations are summarized in the current review. In addition, the knowledge regarding the immunological as well as biochemical characteristics of mustard allergens that have been known till date and their cross-reactivity with other food allergens have also been discussed here. Notably, mustard may also be present as a hidden allergen in foods; therefore, it is important to recognize food products that may contain mustard as it may pose potential risk for the allergic individuals. Additionally, the better understanding of the underlying mechanism in mustard allergy is a prerequisite for the development of specific therapeutic procedures. Conclusively, mustard sensitivity should be routinely tested in patients with idiopathic anaphylaxis for the safety of the allergic patients.