Kidney-bean (Phaseolus Vulgaris) Dependent, Exercise-induced Anaphylaxis in Patients Comorbid with Mugwort (Artemisia Vulgaris) Pollinosis.

Background: The cross-reactive allergen between mugwort (Artemisia vulgaris) and kidney bean (Phaseolus vulgaris) has not yet been identified.Methods: A total of 24 patients were included in this study. The sera of patients were analyzed for the concentrations of specific IgE antibodies. The allergenicity and cross-reactivity were investigated by Western blotting and immunoblot inhibitory experiments.Results: The immunoblotting indicated the binding of patients' IgE to crude mugwort extract at ~26 kDa protein (15 cases), ~60 kDa (15 cases), and 10-15 kDa proteins (12 cases). The results of the immunoblot-inhibition assay showed that kidney bean seed extract inhibited specific IgE binding to mugwort at 10-15 kDa, ~26 kDa, and ~60 kDa in 4 (16.7%), 1 (4.2%) and 2 (8.3%) cases, respectively. On the other hand, mugwort extract was demonstrated to inhibit specific IgE binding to kidney bean seed at 10-15 kDa, 15-20 kDa, ~30 kDa, and 60 kDa in 1 (4.2%), 3 (12.5%), 4 (16.7%), and 3 (12.5%) cases, respectively.Conclusion: The 26-30 kDa, 10-15 kDa, and 60 kDa proteins are potential causative agents of the cross-reactivity between mugwort and kidney beans. The findings of this study improved the current understanding on the allergenicity of kidney beans and would provide insights into the refinement of treatment strategy for anaphylaxis.

Induction of Peanut Allergy Through Inhalation of Peanut in Mice.

Peanut (PN) allergy is a common life-threatening disease; however, our knowledge on the immunological mechanisms remains limited. Here, we describe the first mouse model of inhalation-driven peanut allergy. We administered PN flour intranasally to naïve wild-type mice twice a week for 4 weeks, followed by intraperitoneal challenge with PN extract. Exposure of mice to PN flour sensitized them without addition of adjuvants, and mice developed PN-specific IgE, IgG1, and IgG2a. After challenge, mice displayed lower body temperature and other clinical signs of anaphylaxis. This inhalation model is an ideal system to allow for future examination of immunological mechanisms critical for the development of PN allergy.

Food-dependent, exercise-induced anaphylaxis in a patient allergic to peach.

Determining the single factor that triggered anaphylactic shock can be challenging. We present an interesting case of a 25-year-old female patient with recurrent anaphylactic reactions developing after eating various foods, particularly in presence of co-factors of allergic reactions. Symptoms occurred after consumption of various kinds of foods - peach, pancakes with cottage cheese and fruit, a meal from a Chinese restaurant - all eaten on other occasions without symptoms. During diagnosis, skin prick tests were negative for all tested allergen extracts (both inhalatory and food) from Allergopharma. Prick by prick tests were positive for the peach - wheal diameter - 6 mm, nectarine - 4 mm (histamine 4 mm, negative control 0 mm). Increased levels of asIgE were found for allergens of peach (0.55 kU/L).Open challenge test with one mid-size peach combined with the physical exercise challenge test was positive. ImmunoCAP ISAC test indicated increased levels of IgE specific for the lipid transfer protein (LTP) for walnut (nJug r 3), peach (Pru p 3), wheat (rTri a 14) and plane tree (rPla a 3). The patient was diagnosed with food-dependent, exercise-induced anaphylaxis associated with an allergy to lipid transport proteins (LTPs).

Plasma and urine metabolite profiling reveals the protective effect of Clinacanthus nutans in an ovalbumin-induced anaphylaxis model: 1H-NMR metabolomics approach.

The present study sought to identify the key biomarkers and pathways involved in the induction of allergic sensitization to ovalbumin and to elucidate the potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key requisites for the induction of anaphylaxis reaction. Sensitized rats treated with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive correlation with the normal group and was negatively related to the induced group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and Genomes (KEGG) reveals the protective effect of C. nutans extract against ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism (choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2-propanediol), amino acid metabolism (betaine, N,N-dimethylglycine, methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In summary, this study reports for the first time, C. nutans water extract is a potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative analytical tool to explicate the mechanism of action of anaphylaxis.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

BACKGROUND: Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. METHODS: We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. RESULTS: We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. CONCLUSIONS: Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis.

Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice.

INTRODUCTION: Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen-peptide administration on immune response are unclear. In the present study, we tested the effects of collagen-peptide ingestion on allergic response and the effects of collagen-derived oligopeptides on CD4+ T-cell differentiation. METHODS: BALB/c mice fed a collagen-peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4+ T cells were stimulated with anti-CD3 and anti-CD28 in the presence of collagen-derived oligopeptides, and the expression of IFN-γ, IL-4, and Foxp3 was analyzed. RESULTS: In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA-specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T-helper (Th) type 1 and regulatory T (Treg) cells. In vitro T-helper cell differentiation assays showed that Hyp-containing oligopeptides promoted Th1 differentiation by upregulating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3+ Treg cells in response to antigen stimulation in the presence of TGF-ß. CONCLUSIONS: Collagen-peptide ingestion suppresses allergic responses by skewing the balance of CD4+ T cells toward Th1 and Treg cells and seems to be a promising agent for preventing allergies and inflammatory diseases.

Preventive effects of royal jelly against anaphylactic response in a murine model of cow's milk allergy.

CONTEXT: Royal jelly (RJ) has long been used to promote human health. OBJECTIVE: The current study investigated the preventive effects of RJ against the development of a systemic and intestinal immune response in mice allergic to cow's milk proteins. MATERIALS AND METHODS: Balb/c mice treated orally for seven days with RJ at doses of 0.5, 1 and 1.5 g/kg were sensitized intraperitoneally with ß-lactoglobulin (ß-Lg). Serum IgG and IgE anti-ß-Lg were determined by an enzyme-linked immunosorbent assay (ELISA). Plasma histamine levels, symptom scores and body temperature were determined after in vivo challenge to ß-Lg. Jejunums were used for assessment of local anaphylactic responses by an ex vivo study in Ussing chambers and morphologic changes by histological analysis. RESULTS: RJ significantly decreased serum IgG (31.15-43.78%) and IgE (64.28-66.6%) anti-ß-Lg and effectively reduced plasma histamine level (66.62-67.36%) (p < 0.001) at all the doses tested. Additionally, no clinical symptoms or body temperature drops were observed in RJ-pretreated mice. Interestingly, RJ significantly reduced (p < 0.001) intestinal dysfunction by abolishing the secretory response (70.73-72.23%) induced by sensitization and prevented length aberrations of jejunal villi by 44.32-59.01% (p < 0.001). DISCUSSION AND CONCLUSIONS: We speculate that using RJ may help prevent systemic and anaphylactic response in allergic mice. These effects may be related to its inhibitory effects on the degranulation of mast cells.

Sinomenine-induced histamine release-like anaphylactoid reactions are blocked by tranilast via inhibiting NF-κB signaling.

Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays. The levels of histamine, leukotriene B4 (LTB4) and IL-33 in plasma were detected by UHPLC-SPE-MS, ELISA and immunohistochemistry assays, respectively. The results demonstrated that SIN significantly induced both systemic and local HRARs in rats, showing significant decrease of body temperature, increases in vascular permeability in skin, injury of lung tissues and mast cell infiltration and IL-33 expression in skin and lung tissues. Mechanistic study showed that tranilast could prevent SIN-triggered HRARs via inhibition of H1 receptor gene expression and NF-κB signaling. Our findings provide evidence that mast cell membrane stabilizers and H1 receptor blockers effectively prevent SIN-induced HRARs, and cromolyn, cetirizine and tranilast can be used in the clinic for the management of HRARs induced by ZQFTN.

Inhibitory effects of norlignans isolated from Anemarrhena asphodeloides on degranulation of rat basophilic leukemia- 2H3Cells.

Anemarrhena asphodeloides is known to suppress inflammation and lower various fevers. To determine the active component of A. asphodeloides, ethanol (EtOH) extract of A. asphodeloides rhizomes was fractionized. The compounds isolated from the dichloromethane (CH2Cl2) soluble fraction were identified as 4'-O-methylnyasol (1), nyasol (2), 3″-methoxynyasol (3), 3″-hydroxy-4″-methoxy-4″-dehydroxynyasol (4), 4-hydroxybenzaldehyde (5), and 4-hydroxyacetophenone (6). The four norlignans (1-4) potently inhibited the release of ß-hexosaminidase from immunoglobulin E (IgE)/dinitrophenol-conjugated bovine serum albumin (DNP-BSA)-treated rat basophilic leukemia (RBL)-2H3 and A23187 plus phorbol 12-myristate 13-acetate co-treated isolated rat primary mast cells, as markers of degranulation and histamine release. The intraperitoneal treatment with the EtOH extract significantly suppressed the fetal reaction, and serum histamine release induced by compound 48/80 in mice. These results suggest that the four active norlignan compounds and the EtOH extract of A. asphodeloides may have potential to be developed as medicines for the treatment of allergies by inhibiting the activation of mast cells.

Birch pollen immunotherapy inhibits anaphylaxis to the cross-reactive apple allergen Mal d 1 in mice.

BACKGROUND: Cross-reactive apple allergy is a common co-morbidity of birch pollen allergy, caused by the presence of a Bet v 1 homologue allergen in apple, Mal d 1. Treatment of tree pollen hay fever by immunotherapy is well established, but its effect on the accompanying apple allergy is debated. OBJECTIVE: To establish a mouse model of birch pollen induced cross-reactivity to Mal d 1 and investigate the effect of birch pollen immunotherapy on the cross-reactivity to Mal d 1. METHODS: Respiratory allergy was induced in Balb/c mice by intraperitoneal exposure to alum-adsorbed birch pollen extract (BPE) in combination with short or prolonged intranasal exposure to BPE. To evaluate the response to Mal d 1, mice were exposed intraperitoneally to Mal d 1. Immunoglobulin responses and cytokine production by splenocytes were measured by ELISA. Allergic symptoms were evaluated by measuring airway hyper-reactivity and hypothermia as a surrogate marker for anaphylaxis. Immunotherapy was performed subcutaneously with alum-adsorbed BPE. RESULTS: Mice exposed to BPE develop cross-reactive IgE to Mal d 1. Early after exposure to BPE, this response is still weak and does not yet translate into anaphylaxis. Interestingly, later re-challenge with BPE increased cross-reactivity to a level where Mal d 1 exposure induced anaphylaxis. Cross-sensitization can also be induced by systemic Mal d 1 exposure. Birch pollen immunotherapy significantly reduced the anaphylactic response of mice to Mal d 1. CONCLUSION & CLINICAL RELEVANCE: A mouse model mimicking birch pollen induced cross-reactivity to Mal d 1 was successfully established. In this model, birch pollen immunotherapy significantly ameliorated the anaphylaxis induced by Mal d 1. Our experimental data suggest that boosting of Mal d 1 recognizing immunoglobulins by BP SCIT is important for the amelioration of apple allergy in human.

Identification of wheat sensitization using an in-house wheat extract in Coca-10% alcohol solution in children with wheat anaphylaxis.

BACKGROUND: Identification of wheat sensitization by a skin prick test (SPT) is essential for children with wheat-induced anaphylaxis, since oral food challenge can cause serious adverse effects. Wheat allergens are both water/salt and alcohol soluble. The preparation of wheat extract for SPT containing both water/salt and alcohol soluble allergen is needed. OBJECTIVE: To determine if a wheat extract using Coca's solution containing 10% alcohol (Coca-10% EtOH), prepared in-house, contians both water/salt and alcohol soluble allergens. METHODS: Serum of children with a history of anaphylaxis after wheat ingestion was used. Wheat flour was extracted in Coca-10% alcohol solution. An SPT with both commercial and in-house wheat extracts was performed as well as specific IgE (sIgE) for wheat and omega-5 gliadin. Direct and IgE inhibition immunoblots were performed to determine serum sIgE levels against water/salt as well as alcohol soluble (gliadins and glutenins) allergens in the extracts. RESULTS: Six children with history of wheat anaphylaxis had positive SPT to both commercial and in-house extracts. They also had different levels of sIgE against wheat and omega-5 gliadin allergens. The results of direct immunoblotting showed all tested sera had sIgE bound to ~35 kDa wheat protein. Further IgE inhibition immunoblotting identified the ~35 kDa wheat protein as gliadin but not gluten allergen. CONCLUSION: The in-house prepared Coca-10% EtOH solution could extract both water/salt and alcohol soluble allergens. The ~35 kDa gliadin appears to be a major wheat allergen among tested individuals.

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

ETHNOPHARMACOLOGICAL RELEVANCE: Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. MATERIALS AND METHODS: Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. RESULTS: Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. CONCLUSION: Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma.

IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

BACKGROUND: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. METHODS: Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. RESULTS: Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA /l is significantly associated with the development of systemic reactions to peanut.

Inhibition of three novel Radix Scutellariae extracts on immediate hypersensitivity.

BACKGROUND: Radix Scutellariae, a few papers reported its pharmacology activities including alleviate small intestines smooth muscles spasm, sedation, antihypertensive effect. However, the inhibition of its different organic extracts on immediate hypersensitivity has not bee researched. MATERIALS AND METHODS: To investigate the anti-immediate hypersensitivity of three extracts including ethanol extracts, acetone extracts, ethyl acetate extracts from Radix Scutellariae, four pharmacological screening model were chose, such as 4-Aminopyridine induced pruritus model, histamine-induced mouse paw edema model, PCA(passive cutaneous anaphylaxis) in ear of mouse, activie cutaneous anaphylaxismouse (mouse ear edema test), furthermore, total IgE level in the sensitized mice serum was evaluated deeply. RESULTS: Ethanol group at 1.42 g/kg and 0.71 g/kg could greatly decrease the licking number to 1.2 and 12.7 respectively; also keep mice paw swelling at 0.29 ml and 0.51 ml at 15 min after injection of histamine. Both ear passive cutaneous allergic reaction and active cutaneous anaphylaxis-ear swelling test demonstrated that ethanol group exhibit great inhibition on immediate hypersensitivity.Low IgE level was found in ethanol group, but high in other two groups. CONCLUSION: The ethanol extracts exhibits obvious strong inhibition, however, the acetone ones and ethyl acetate showed a little.

Preventive effects of skullcap (Scutellaria baicalensis) extract in a mouse model of food allergy.

ETHNOPHARMACOLOGICAL RELEVANCE: Food allergy, which accompanies acute symptoms such as pruritus, vomiting, diarrhea, and lethal anaphylactic shock is an increasing clinical problem. Skullcap (Scutellaria baicalensis Georgi) has been widely used as a traditional herbal medicine to treat inflammation, cancer, and allergy, but its effects in treating food allergy are not yet known. MATERIALS AND METHODS: To examine the effect of skullcap on food allergy, female BALB/c mice were sensitized with 20 µg OVA and 2mg alum by intraperitoneal injection on day 0. From day 17, mice were orally challenged with OVA (50 mg) in saline every 3 days, for a total of six times. To investigate the preventive effect, skullcap (25 mg/kg) was orally administered every day from day 17 to 34. RESULTS: Food allergy symptoms were evaluated by the criteria for diarrhea, anaphylactic response, and rectal temperature. Severe symptoms of food allergy were observed in the sham group (diarrhea, 3 points; anaphylactic response, 2.6 points; rectal temperature, -8.36 °C. In contrast, the skullcap treatment group had a significantly suppressed OVA-induced anaphylactic response (1.3 points) and rectal temperature (-4.76°C). Moreover, both OVA-specific IgE, Th17 cytokine (IL-17), and Th2-related cytokines (IL-4, IL-5, IL-10, and IL-13), which increased with food allergy, were significantly inhibited by skullcap treatment. CONCLUSION: We demonstrate that the administration of skullcap attenuates OVA-induced food allergy symptoms through regulating systemic immune responses of Th cells. These results indicate that skullcap may be a potential candidate as a preventive agent for food allergy.

A rapid and low-cost approach to evaluate the allergenicity of herbal injection using HPLC analysis.

Herbal medicines have ever been thought harmless, but it is obviously not true. Many adverse reports emerged with the development of their popular application in the world. Allergic reactions, especially serious immediate hypersensitivity, frequently occurred when herbal injections were used in clinic and made this ever prevailing agent nearly disappear in China. The aim of this study is to establish a rapid and economical method for the prediction of the allergenicity of herbal injections. Ovalbumin (OVA) and four other herbal injections, in which two of them were well known for their allergenicity, were selected to sensitize and stimulate the animals. Serotonin in the animal serum was detected with HPLC to reflect the anaphylactic response and compared with the other cytokines which could mediate the anaphylaxis, including histamine, IgE and ß-hexosaminidase. The results suggest that serotonin can be detected quickly and has good correlation with the other allergy-related cytokines. It is a promising way for predicting the allergenicity of the herbal injections and those complicated natural products.

Cross-allergic reactions to legumes in lupin and fenugreek-sensitized mice.

Several legumes may induce allergy, and there is extensive serological cross-reactivity among legumes. This cross-reactivity has traditionally been regarded to have limited clinical relevance. However, the introduction of novel legumes to Western countries may have changed this pattern, and in some studies cross-allergy to lupin has been reported in more than 60% of peanut-allergic patients. We wanted to explore cross-reactions among legumes using two newly established mouse models of food allergy. Mice were immunized perorally with fenugreek or lupin with cholera toxin as adjuvant. The mice were challenged with high doses of fenugreek, lupin, peanut or soy, and signs of anaphylactic reactions were observed. Cross-allergic mechanisms were investigated using serum mouse mast cell protease-1 (MMCP-1), antibody responses, immunoblotting and ex vivo production of cytokines by spleen cells. Signs of cross-allergy were observed for all the tested legumes in both models. The cross-allergic symptoms were milder and affected fewer mice than the primary allergic responses. The cross-allergy was reflected to a certain extent in the antibody and T-cell responses, but not in serum MMCP-1 levels. Cross-allergy to peanut, soy, fenugreek and lupin was observed in lupin-sensitized and fenugreek-sensitized mice. Differences in serological responses between primary allergy and cross-allergy might be due to mediation through different immune mechanisms or reflect different epitope affinity to IgE. These differences need to be further investigated.