High prevalence of lupin allergy among patients with peanut allergy: Identification of γ-conglutin as major allergen.

BACKGROUND: Lupin is a protein-rich legume with a growing presence in the food market worldwide. With increased consumption, lupin allergy (LA) reports are also rising. Uncertainties exist on the cross-reactivity between peanut and lupin, the allergenic potential of different lupin species, and sensitization patterns among different populations. OBJECTIVE: To evaluate the molecular basis of LA and to determine lupin allergens from 3 different species that may be involved in peanut allergy (PA) cross-reactivity. METHODS: A total of 43 subjects with PA, those with LA, or controls without food allergy were evaluated with skin prick tests (SPTs) and specific IgEs (sIgEs). Lupin-sensitized subjects were offered a lupin oral food challenge (OFC). Immunoblots and enzyme-linked immunosorbent assays were performed on sera from lupin-sensitized subjects. RESULTS: In this study, 44% of the PA subjects were confirmed to have LA by OFC. Anaphylaxis was the most frequent manifestation after lupin consumption, with a minimal eliciting dosage of 1 g lupin flour. There was no difference in lupin sIgE or SPT wheal size between lupin-sensitized and confirmed LA subjects or in the severity of symptoms among confirmed LA subjects. Sera from lupin-sensitized subjects uniformly reacted to all 3 different lupin species. Immunoblotting and enzyme-linked immunosorbent assays revealed immunoglobulin E binding to α- and γ-conglutin in all analyzed sera, whereas α- and ß-conglutin recognition was variable. CONCLUSION: Our findings reveal a high prevalence of LA among PA subjects, emphasizing lupin must be labeled as an allergen in foods. Owing to high variability in lupin-sIgE and lupin-SPT results, LA diagnosis may require OFC. In our population, γ-conglutin is the major allergen of lupin.

Lupine allergens: Clinical relevance, molecular characterization, cross-reactivity, and detection strategies.

Lupine is commonly utilized as a technological food and ingredient in a great variety of processed products (snacks, bakery, meat, and dairy products) principally owing to its nutritional value and technological properties. However, its ingestion, even at trace amounts (in the range of mg protein per kg of food), can lead to severe adverse reactions in allergic individuals. Lupine belongs to the Leguminosae family, having the conglutins (α-, ß-, δ-, and γ-) as allergens, among other proteins. Cross-sensitization of lupine-sensitized individuals with other legume species, mainly peanut, can occur, but the associated clinical reactivity is still unclear. The protection of the sensitized individuals should depend on an avoidance diet, which should rely on the compliance of food labeling and, as such, on their verification by analytical methods. Food processing, such as heat treatments, has an important influence on the structural properties of lupine proteins, altering their detectability and allergenicity. In this review, different aspects related with lupine allergy are described, namely, the overall prevalence, clinical relevance, diagnosis, and treatment. The characterization of lupine allergens and their potential cross-reactivity with other legumes are critically discussed. The effects of food matrix, processing, and digestibility on lupine proteins, as well as the available analytical tools for detecting lupine at trace levels in foods, are also herein emphasized.

Lupine as a potential agent against diet-induced obesity through adenosine monophosphate-activated protein kinase pathway: crude oil versus nanoemulsion formulations

Obesity represents a major challenge to the pharmaceutical community due to the minimal availability of anti-obesity drugs and the drawbacks of current weight-loss agents. The study described herein presents lupine oil, in two pharmaceutical formulations, as a potential anti-obesity agent via its effect on different physiological, biochemical, and hormonal parameters. Rats were divided into two groups; one group was continued on a standard commercial rodent diet and served as the non-obese control. The other group was fed a high-fat diet for 7 weeks to prepare an obese rat model. Then, the obese rats were divided into groups to receive 100 mg/kg of the crude lupine oil or nanoemulsion for 10 or 20 days. Lupine oil showed a potent body weight-reducing effect and improved insulin resistance. The oil altered obesity-induced hyperlipidemia and it enhanced the leptin/adiponectin/AMPK hormonal system in epididymal fat, serum, and liver, to which all the above physiological activities could be attributed. The nanoemulsion formulation of lupine oil significantly amplified the activity for all the above physiological and hormonal parameters when compared to the crude oil formulation. Lupine oil nanoemulsion could be used as a potential drug against diet-induced obesity.

Allergic reaction to undeclared lupin in a chocolate

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Intoxicación por "agua de cocción de chochos" / Lupin beans (chochos) poisoning

Se presenta un caso clínico poco habitual de intoxicación secundaria a ingesta de alcaloides procedentes de altramuces, consumidos con frecuencia por su valor nutricional. Se describen los efectos adversos más frecuentes tras la ingesta de lupino, que incluyen: síntomas anticolinérgicos y alteraciones del SNC leves y se expone el manejos de su intoxicación. El caso ilustra la dificultad que entraña el diagnóstico y la importancia de una buena anamnesis y exploración fisica detalladas (AU)

An unusual clinical case of secondary poisoning after intake of lupine alkaloids, often consumed for its nutritional value is presented. Most frequent side effects after intake of lupine are described, including anticholinergic symptoms and mild CNS disorders and management of poisoning is discussed. The case illustrates the difficulty of diagnosis and the importance of a good history and detailed phusical examination (AU)

Development and validation of an LC-MS/MS method for the detection of phomopsin A in lupin and lupin-containing retail food samples from the Netherlands.

Phomopsins (PHO) are mycotoxins produced by the fungus Diaporthe toxica (also referred to as Phomopsis leptostromiformis). Lupin is the most important host crop for this fungus and PHO are suspected as cause of lupinosis, a deadly liver disease, in sheep. Lupin is currently in use to replace genetically modified soy in many food products available on the European market. However, a validated method for analysis of PHO is not available until now. In this work, a dilute-and-shoot LC-MS/MS-based method was developed for the quantitative determination and identification of phomopsin A (PHO-A) in lupin and lupin-containing food. The method involved extraction by a mixture of acetonitrile/water/acetic acid (80/20/1 v/v), dilution of the sample in water, and direct injection of the crude extract after centrifugation. The method was validated at 5 and 25 µg PHO-A kg(-1) product. The average recovery and RSD obtained were 79% and 9%, respectively. The LOQ (the lowest level for which adequate recovery and RSD were demonstrated) was 5 µg PHO-A kg(-1). Identification of PHO-A was based on retention time and two transitions (789 > 226 and 789 > 323). Using the average of solvent standards from the sequence as a reference, retention times were all within ± 0.03 min and ion ratios were within ± 12%, which is compliant with European Union requirements. The LOD (S/N = 3 for the least sensitive transition) was 1 µg PHO-A kg(-1) product. Forty-two samples of lupin and lupin-containing food products were collected in 2011-2012 from grocery stores and internet shops in the Netherlands and analysed. In none of the samples was PHO-A detected.

Characterization of the sensitization profile to lupin in peanut-allergic children and assessment of cross-reactivity risk.

BACKGROUND: Case reports of allergy to lupin, due to primary sensitization or cross-reactions with other legumes, are increasing as a consequence of the augmented use of lupin flour in bakery, pasta formulations and other food items. The main allergens that have been associated with the sensitization to lupin are α- and ß-conglutins and, to a lesser extent, γ- and δ-conglutin, but no conclusive data are available so far. The aim of this study was to characterize the sensitization pattern to lupin in a group of 12 Italian children allergic to peanut and identify the specific lupin proteins involved in the cross-reactivity with peanut. METHODS: The immunochemical cross-reactivity among peanut and lupin was evaluated by both in vitro immunoblotting and in vivo fresh food skin prick test (FFSPT). RESULTS: The results showed that ß-conglutin was recognized by cutaneous IgEs from 7/12 peanut-allergic children in FFSPT and serum IgEs from 5/12 in immunoblotting, while 4/12 and 8/12 patients tested positive to γ-conglutin in FFSPT and immunoblotting, respectively. No significant immunoreactive responses were observed to α- and δ-conglutins under non-reducing conditions, but they were bound in FFSPT by the sera of 5/12 and 3/12 patients, respectively. CONCLUSION: In this group of allergic children, ß-conglutin has been identified as the major lupin allergen involved both in vitro and in vivo cross-reactivity with peanut proteins. The role of γ-conglutin in the cross-reactivity between lupin and peanut proteins was also relevant and clear, despite the observed unspecificity of the immunoblotting responses.

[Anticholinergic syndrome after intoxication by lupine seeds (Tourmos)]. / Syndrome anticholinergique après intoxication par des graines de lupin (Tourmos).

INTRODUCTION: Yellow lupine seeds (Tourmos) are frequently used as snack in Lebanon but their potential toxicity is extremely rare (five published cases) and often undiagnosed. CASE REPORTS: Two patients presented with anticholinergic syndrome (mydriasis, mouth dryness, palpitations, general malaise) after ingestion of 200-500 g of bitter lupine seeds (not soaked enough in water). No other cause of intoxication was found, and symptoms disappeared spontaneously in 24-36h. DISCUSSION: Yellow lupine seeds need a long preparation (boiling then soaking with several changes of water) to debitter before consumption. The spontaneous bitter taste is mainly due to the presence of a toxic substance with anticholinergic properties, lupanine. An insufficient preparation or a preference for bitter lupin can result in intoxication.

Sensitization to lupine flour: is it clinically relevant?

BACKGROUND: Lupinus angustifolius (blue lupine) is used for human and animal consumption. Currently, the lupine content in bread varies from 0% to 10% and from 0.5% to 3% in pastry. Although lupine flour is present in many products, anaphylaxis on lupine flour is rarely seen. OBJECTIVE: The aim of our study was to determine the clinical relevance of sensitization to lupine flour. METHODS: From October 2004 until October 2005, we performed skin prick tests (SPT) with lupine flour, peanut and soy extracts in consecutive patients attending our allergy clinic with a suspected food allergy. In patients sensitized to lupine flour, double-blind placebo-controlled food challenges (DBPCFC) were performed and specific IgE was measured. RESULTS: We tested 372 patients. SPTs with peanut, soy and lupine flour were positive in 135, 58 and 22 patients, respectively. Nine patients with sensitization to lupine flour underwent DBPCFC, which was negative in eight cases. In contrast, one patient experienced significant symptoms. Four of these nine patients suspected lupine by history. Two other patients with a positive history to lupine declined from challenges. In these patients, a 3-day dietary record showed that they could consume lupine without symptoms. Specific IgE in the serum was positive for L. angustifolius, peanut and soy in all nine patients. CONCLUSION: These results demonstrate that clinical lupine allergy is very uncommon, even in the presence of sensitization to lupine flour. The estimated prevalence of lupine allergy, among patients with a suspected food allergy, referred to a tertiary allergy centre in the Netherlands is 0.27-0.81%. In most, although not all cases, sensitization is not clinically relevant and is most likely caused by cross-sensitization to peanut. In selected cases, eliciting doses are low, making significant reactions possible.

Recurrent anaphylaxis due to lupin flour: primary sensitization through inhalation.

Allergic reactions to lupin have increased in parallel with the growing use of lupin flour by food manufacturers. We studied a patient with recurrent anaphylaxis to manufactured foods and a history of rhinitis-asthma related to lupin inhalation and legume tolerance. Skin prick tests with airborne and food allergens, specific immunoglobulin (Ig) E determinations, and an inhalation exposure test to ground lupin were carried out. Lupin allergens and cross-reactivity with other legumes were also studied using sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting/immunoblotting inhibition. The skin tests and specific IgE were positive for lupin and vetchling and negative for other legumes. The presence of lupin flour in the implicated foods was confirmed. Immunoblotting showed multiple IgE-binding bands (10-40 kDa) for lupin and vetchling but not for peanut, pea, or soy extracts. Immunoblotting inhibition demonstrated intense lupin-vetchling cross-reactivity. We present a case of recurrent anaphylaxis due to lupin flour as a hidden food allergen with primary sensitization due to exposure to ground lupin via inhalation. We found cross-reactivity between lupin and vetchling but not other legumes.

Gluten-free food as source of hidden allergen (lupine).

A woman, 68 yrs, developed an anaphylactic reaction after tasting a few pieces of gluten-free pasta. She was not celiac but was preparing a meal for her celiac nephew. The culprit pasta contained lupine flour and lupine proteins. Prick test with lupine extract was positive. ELISA and immunoblot analysis showed the presence of specific IgE to lupine in patient's serum.

Lupin allergy and lupin sensitization among patients with suspected food allergy.

BACKGROUND: Lupin, a legume with good nutritional value, is used in food production today, most often in bakery products. Lupin sensitization is often seen among patients with reactions to legumes, but the number of reports describing lupin anaphylaxis is also increasing. OBJECTIVE: To investigate the occurrence of lupin sensitization, cross-reactivity, and lupin allergy among patients with suspected food allergy in Finland, where lupin is a labeled ingredient in few products. METHODS: The occurrence of positive skin prick test (SPT) reactions to lupin seed flour was studied among 1522 patients with suspected food allergy from November 1, 2005, through December 31, 2007. Clinical histories and diagnostic SPT results were analyzed among patients with positive SPT results to lupin. For 1 patient, ImmunoSpot and lupin radioallergosorbent test inhibition methods were used. RESULTS: Lupin sensitization was shown in 25 of 1522 patients (1.6%), and probable lupin allergy was diagnosed in 7 of 25 patients, in whom the clinical symptoms varied from anaphylaxis and respiratory symptoms to contact urticaria and itchy mouth. Cross-reactions or concurrent reactions to other legumes were seen in 18 of 25 patients. CONCLUSIONS: Clinically relevant lupin allergy often occurs in patients without atopic background or other food allergies, although lupin sensitization most commonly seems to represent cross-reactivity to other legumes. The occurrence of lupin allergy in a country where lupin has not been traditionally used is surprisingly common, suggesting that short-term use of modest amounts of lupin can cause serious allergic reactions.

The prevalence of sensitization to lupin flour in France and Belgium: a prospective study in 5,366 patients, by the Allergy Vigilance Network.

OBJECTIVES: To determine the prevalence of sensitization to lupin flour in patients consulting allergists, in order to evaluate the risk of primary and secondary allergies to lupin. METHODS: A prospective study carried out by members of the Allergy Vigilance Network, using prick-tests with a commercial lupin flour extract in patients with various allergic symptoms. The study design classified patients into four groups: peanut allergy, current atopic disease, latent atopy, no atopy. Data were collected and analysed by Network coordinators. RESULTS: Over a two-month period, 88 French and Belgian allergists tested 5,366 patients: 2,680 children and 2,686 adults aged over 16 years. Of the 2,680 children, 11.15% presented with peanut allergy. The frequency of cross-reactivity with lupin was 17.1% for patients with peanut allergy, 2.5% for children with current atopic disease and 1.7% for healthy children with latent atopy. In the 2,686 adults, peanut allergy was diagnosed in 1.86% of patients with cross-reactivity to lupin in 14.6%. Sensitization to lupin was detected in 3.7% of patients with current atopic disease and in 1.8% of those with latent atopy. CONCLUSION: The relative frequency of latent sensitisation to lupin in patients of all ages presenting with atopic disease is a new factor indicating the likelihood of an increase in primary food allergies to lupin flour. This justifies the recent decision requiring mandatory labelling of lupin, and shows the need to inform consumers who may be unaware that this ingredient is being used increasingly. Sensitization to lupin should be searched by prick-tests in any case of peanut allergy. Prick-test to lupin may be valuable whenever a food allergy is suspected when no current food allergens have been identified.

A mouse model of lupin allergy.

BACKGROUND: Lupin has been introduced as a new food ingredient in an increasing number of European countries, resulting in reports of allergic reactions mostly due to cross-reactions in peanut-allergic individuals. Some cases of primary lupin allergy have also been reported. OBJECTIVE: The aim of our study was to develop a food allergy model of lupin in mice with anaphylaxis as the endpoint and further, to develop an approach to estimate the allergen dose inducing maximal sensitization using a statistical design requiring a limited number of animals. METHODS: Mice were immunized by intragastric gavage using cholera toxin as an adjuvant. A two-compartment response surface design with IgE as the main variable was used to estimate the maximal sensitizing dose of lupin in the model. This estimated dose was further used to evaluate the model. The mice were challenged with a high dose of lupin and signs of an anaphylactic reaction were observed. Antibody reactions (IgE and IgG2a), serum mast cell protease [mouse mast cell protease-1 (MMCP-1)] and ex vivo production of cytokines (IL-4, IL-5 and IFN-gamma) by spleen cells were measured. An immunoblot with regard to IgE binding was also performed. RESULTS: The dose that elicited the maximal sensitization measured as IgE was 5.7 mg lupin protein per immunization. Mice that received this dose developed anaphylactic reactions upon challenge, IgE against several proteins in the lupin extract, and high levels of MMCP-1, and showed a general shift towards a T-helper type 2 response. Post-challenge serum MMCP-1 levels corresponded to the seriousness of the anaphylactic reactions. CONCLUSION: We have established a mouse model with clinical symptoms of lupin allergy, with an optimized dose of lupin protein. A statistical design that can be used to determine an optimal immunization dose with the use of a minimum of laboratory animals is described.

Assessment of the tolerance to lupine-enriched pasta in peanut-allergic children.

BACKGROUND: Reports of allergy to lupine derivatives (as de novo sensitization or cross-reactivity in subjects allergic to peanut) are increasing as their use in food products increases. OBJECTIVES: The aim of this study was to assess: (1) lupine tolerance in a group of children allergic to peanut, using lupine enriched-pasta instead of raw flour as has been done in previous clinical studies; (2) whether technological treatments of lupine modify its cross-reactivity or co-sensitization with peanut; (3) the role of lupine seed proteins in sensitization, and (4) to identify the eliciting doses (EDs) by using double-blind, placebo-controlled food challenges (DBPCFC). METHODS: Twelve patients with a history of clinical allergic reactions to peanut were evaluated by skin prick tests (SPTs), the ImmunoCAP test, immunoblotting, and DBPCFC. The 12 selected subjects were included in a trial where lupine-enriched pasta and placebo pasta were administered in a DBPCFC protocol. RESULTS: Positive clinical reactions were observed in two children, the EDs being 0.2 and 6.4 g of pasta, corresponding to 50 mg and 1.6 g of lupine proteins, respectively. Beta-conglutin was the protein most involved in SPT positivity. CONCLUSION: Lupine-enriched pasta can be tolerated by most subjects suffering from peanut allergy, but a sizeable minority (2/12 of them in this case) can develop potentially dangerous clinical reactions. Information about possible reactions to lupine derivatives by those allergic to peanuts must be included in the labelling of lupine-enriched products to protect consumers at risk.

Clinical relevance of sensitization to lupine in peanut-sensitized adults.

BACKGROUND: The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). METHODS: Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. RESULTS: Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. CONCLUSION: In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness.

Lupin sensitization and clinical allergy in food allergic children in Norway.

AIM: The aim of the present pilot study was to investigate to what extent children in Norway sensitized to lupin had clinical lupin allergy, and to compare sensitization to lupin with sensitization to other legumes. METHODS: Thirty-five children with food allergy referred to a national referral hospital were evaluated with skin prick test (SPT) and analysis of serum-specific IgE to lupin, peanut, pea and soy. The children with positive SPTs to lupin were offered oral food challenges with lupin flour. RESULTS: Fifteen children (43%) had positive SPT and 17 children (49%) had serum-specific IgE to lupin. Ten SPT-positive children underwent oral food challenges and one experienced an allergic reaction to lupin flour. This child was one of six challenged children with IgE antibodies to peanut >15 kU(A)/L. There was a strong relationship between positive SPT to lupin flour and positive SPT to soy and between positive SPT to lupin and specific IgE to soy, pea and peanut. CONCLUSIONS: Children with sensitization to lupin are not likely to have a clinical lupin allergy. Avoidance of lupin on the basis of lupin sensitization or peanut allergy would lead to unnecessarily strict diets. Food challenge is currently necessary to diagnose lupin allergy.