Gene/Protein Disease Symptom Drug Enzyme Compound
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A high percentage of birch pollen allergic patients experiences food hypersensitivity reactions after ingestion of several fruits and vegetables. Previous work demonstrated common epitopes on an allergen of Mr 18,000 from sweet cherry (Prunus avium) and Bet v 1, the major allergen from birch pollen. N-terminal amino acid sequencing showed a sequence identity of 67% with Bet v 1. Here we report the cloning and cDNA sequencing of this cherry allergen. The entire deduced amino acid sequence described a protein of Mr 17,700 with 59.1% identity to Bet v 1. High degrees of identity in the range of 40 to 60% were also found with related allergens from other kinds of tree pollen and plant foods as well as with stress-induced proteins from food plants such as parsley, potato and soya. The coding DNA of the cherry protein was cloned into vector pET-16b and expressed in E. coli strain BL21(DE3) as a His-tag fusion protein. As shown by SDS-PAGE, the apparent molecular masses of the nonfusion protein and the natural allergen were identical. The fusion protein showed high IgE binding potency when sera from patients allergic to cherry were tested by immunoblotting and enzyme allergosorbent tests. Moreover, it cross-reacted strongly with IgE specific for the natural counterpart and for Bet v 1. The high biological activity of the recombinant fusion protein was further confirmed by the induction of a strong histamine release in basophils from cherry-allergic patients. Since sera from 17/19 of such patients contained IgE against this allergen it was classified as a major allergen and named Pru a 1. Recombinant Pru a 1 mimics most of the allergenic potency of cherry extract and hence could be a useful tool for studying the molecular and immunological properties of pollen related food allergens.
Mol Immunol 1997 Jun
PMID:Molecular cloning, expression and characterization of Pru a 1, the major cherry allergen. 939 65

BACKGROUND: Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. CASE PRESENTATION: The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7-10 days, with each episode lasting for 1-3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. CONCLUSIONS: The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.
Clin Mol Allergy 2004 May 14
PMID:Eosinophilia in a patient with cyclical vomiting: a case report. 1514 61

Food allergy is a hypersensitivity reaction to normally harmless substances and involves humoral immune responses, mediated by immunoglobulin (IgE) synthesized by B lymphocytes, and cellular immune responses mediated by T lymphocytes. An IgE-mediated mechanism leads to clinical symptoms occurring immediately after food ingestion, e. g., "the oral allergy syndrome". For delayed reactions involving the gastrointestinal tract or the skin, the underlying immune mechanisms are less clear. In order to elucidate the cellular response to food allergens, human allergen-specific T cell cultures generated in vitro represent helpful tools. The majority of food allergen-specific CD4(+) T lymphocytes isolated from food-allergic individuals was found to synthesize high levels of IL-4 and IL-13, two cytokines required for initiation of IgE synthesis. Due to selective homing profiles, food-specific T cells seem also to be involved in defining the target organ of the allergic inflammation. Recent data provide evidence that in addition to IgE-mediated inflammation, food allergen-specific T lymphocytes may also cause inflammatory responses independently of IgE-mediated mechanisms.
Mol Nutr Food Res 2004 Nov
PMID:T lymphocytes and food allergy. 1550 77

Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present.
Mol Nutr Food Res 2004 Nov
PMID:Food allergy to apple and specific immunotherapy with birch pollen. 1550 79

According to the recently revised nomenclature for allergy the term "Food Hypersensitivity" is proposed to define a reaction on food exposure causing objectively reproducible symptoms or signs at a dose tolerated by normal subjects. Those reactions to food in which immunologic mechanisms are demonstrated comprise the term "Food Allergy". Immunologic reactions to food in which an immunoglobulin E (IgE)-mediated mechanism is established are defined as IgE-mediated food allergy. This review focuses on IgE-mediated allergic reactions to foods.
Mol Nutr Food Res 2004 Oct
PMID:Diagnosis and therapy of food allergy. 1567 74

Lipid transfer proteins are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have recently been described as true food allergens in the Mediterranean area, where they have been associated with severe allergic reactions to foods in patients without pollen allergy. In this review we analyze their molecular structure, biological function, and clinical relevance in food allergy.
Mol Nutr Food Res 2004 Oct
PMID:Clinical role of lipid transfer proteins in food allergy. 1567 75

Immunoglobulin E (IgE)-mediated food allergy to crustaceans and mollusks is relatively common and affected individuals typically react to a range of different species. The only known major allergen of shrimp was first described over 20 years ago and later identified as the muscle protein tropomyosin. This protein may be useful as a defined and relevant diagnostic marker for allergic sensitization to invertebrate foods. In order to generate an assay reagent suitable for this purpose, tropomyosin from the shrimp Penaeus aztecus (Pen a 1) was produced as a recombinant protein in Escherichia coli and characterized with respect to IgE antibody binding properties in comparison to natural shrimp tropomyosin. Hexahistidine-tagged rPen a 1 accumulated as a predominantly soluble protein in the E. coli expression host and a two-step chromatographic procedure provided a high yield of pure and homogeneous protein. rPen a 1 displayed chromatographic and folding characteristics similar to those of purified natural shrimp tropomyosin. Serum preincubation with serial protein dilutions revealed similar capacity of recombinant and natural tropomyosin to compete with immobilized shrimp extract for IgE binding. rPen a 1 was further shown to extensively and specifically compete for IgE binding to extracts of other crustacean species, house dust mite and German cockroach.
Mol Nutr Food Res 2004 Oct
PMID:Recombinant tropomyosin from Penaeus aztecus (rPen a 1) for measurement of specific immunoglobulin E antibodies relevant in food allergy to crustaceans and other invertebrates. 1567 77

Baker's asthma, food allergy to wheat, and wheat-dependent, exercise-induced anaphylaxis (WDEIA) are different clinical forms of wheat allergy. We investigated the correlation of solubility and digestion stability of wheat allergens with the IgE-reactivity patterns of different patient groups. Three wheat protein fractions were extracted according to their solubility: salt-soluble albumins and globulins, ethanol-soluble gliadins, and glutenins soluble only after treatment with detergents and reducing reagents. Sera from subjects with history of each variant of wheat allergy were characterized by CAP FEIA and immunoblotting. There was a high degree of heterogeneity of recognized allergens between the different subject groups as well as within these groups. However, subjects with WDEIA showed similar immunoglobulin E (IgE)-reactivity patterns to gliadins and especially to a 65 kDa protein. Subjects with baker's asthma as well as the food-allergic subjects had the most intense IgE-reactivity to the albumin/globulin fraction. The latter group additionally showed IgE-reactivity to the other fractions. Divergent results of immunoblotting and CAP-FEIA demonstrated that the detection of wheat-specific IgE highly depends on the applied method, thus the diagnostic tool must be carefully chosen. Most wheat allergens were rapidly digested as analyzed by determination of IgE-reactivity on immunoblots to wheat extracts after simulation of gastric and duodenal digestion. However, ethanol-soluble gliadins were stable to gastric enzymes and exhibit low solubility in gastric and duodenal fluids. Therefore, they are likely to be important in food allergy to wheat.
Mol Nutr Food Res 2004 Oct
PMID:Immunoglobulin E-reactivity of wheat-allergic subjects (baker's asthma, food allergy, wheat-dependent, exercise-induced anaphylaxis) to wheat protein fractions with different solubility and digestibility. 1567 78

Grass allergy is the most common pollinosis in Northern Italy. Some patients with grass allergy show polysensitization against other pollens and plant-derived foods. In these patients oral allergic syndrome (OAS) is frequently associated. To evaluate the correlation between food allergy or food sensitization and specific IgE against panallergens such as Bet v 1 and Bet v 2, we studied 56 children (mean age: 8 years 5 months) suffering from respiratory allergy due to grass pollens were enrolled. Specific IgE against the most important food, inhalant allergen and Bet v 1, Bet v 2 were performed by ImmunoCAP technology (UniCAP 1000, Pharmacia Diagnostics, Uppsala, Sweden). We found 14 children (25%) sensitized to Bet v 1 and 13 (23%) to Bet v 2; in 24 cases (42.3%) a sensitization to at least one of the 2 panallergens was observed. Five of the 14 cases (36%) sensitized to Bet v 1 showed food allergy and 8 (57%) food sensitization; 6 (46%) of the 13 children sensitized to Bet v 2 showed food allergy and 7 (54%) food sensitization; only one case of Bet v 1 specific IgE without food allergy or sensitization was seen. Sixteen subjects (29%) showed food allergy (group A); 20 children (35.5%) multiple sensitizations to inhalant and at least one plant-derived food (group B); 20 subjects (35.5%) only inhalant allergens (group C). Sensitization to Bet v 1 (P<0.03) and Bet v 2 (P<0.009) is from a statistical point of view significantly higher in groups A and B than in group C. In the 16 patients with food allergy hazelnut was the major triggering food (50%), followed by peanut (38%), kiwi (31%), apple and walnut (19%). Specific IgE for Bet v 1 is more associated with nuts and legumes, while Bet v 2 is more related to fresh fruit and vegetables. In conclusion grass pollinosis is frequently associated with polysensitization to other pollen and food allergens. Bet v 1 and Bet v 2 specific IgE are significantly higher in these patients than in patients with grass monosensitization, and this sensitization may be considered a possible risk factors to evolve later into food allergy. Among the offending foods, legumes and the nut group are mostly related to Bet v 1, while vegetables and fresh fruits to Bet v 2.
Mol Immunol 2005 Jun
PMID:Relationship between Bet v 1 and Bet v 2 specific IgE and food allergy in children with grass pollen respiratory allergy. 1582 14

Atopic dermatitis (AD) is a chronic pruritic skin disease affecting up to 15% of children in industrialized countries. AD belongs to the group of allergic disorders that include food allergy, allergic rhinitis, and asthma. A multifactorial background for AD has been suggested, with genetic as well as environmental factors influencing disease development. Genome-wide screens for AD have been completed in four different populations to date. Interestingly, the susceptibility regions identified for AD show little overlap with asthma susceptibility regions, suggesting that, at least in part, separate genes might be involved in the pathogenesis of the different atopic disorders. Instead, some of the identified regions overlap with susceptibility regions for psoriasis, another chronic skin disease. Thus, genes expressed in the skin might play an important role in AD pathogenesis, in addition to genes influencing atopic diatheses. Although no veritable "AD gene" has been identified by positional cloning to date, examples from other complex genetic disorders such as asthma show that this goal is likely to be reached in the near future. Candidate gene studies, on the other hand, have identified 19 genes that were shown to be associated with AD in at least one study. The results of genome-wide screens as well as candidate gene studies are evaluated here in detail.
J Mol Med (Berl) 2005 Sep
PMID:The genetics of atopic dermatitis: recent findings and future options. 1590 88


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