Asunto(s)
Alérgenos/inmunología , Dermatitis Atópica/diagnóstico , Epidermis/metabolismo , Inmunoglobulina E/inmunología , Síndrome de Netherton/diagnóstico , Proteínas Inhibidoras de Proteinasas Secretoras/metabolismo , Adolescente , Niño , Preescolar , Dermatitis Atópica/genética , Dermatitis Atópica/inmunología , Epidermis/patología , Femenino , Finlandia , Alimentos/efectos adversos , Humanos , Inmunoglobulina E/sangre , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Mutación/genética , Síndrome de Netherton/genética , Síndrome de Netherton/inmunología , Profilinas/efectos adversos , Profilinas/análisis , Profilinas/inmunología , Proteínas Inhibidoras de Proteinasas Secretoras/genética , Inhibidor de Serinpeptidasas Tipo Kazal-5Asunto(s)
Brassica napus/inmunología , Brassica rapa/inmunología , Dermatitis Atópica/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Administración Oral , Adolescente , Alérgenos/inmunología , Antígenos de Plantas/inmunología , Niño , Preescolar , Reacciones Cruzadas , Dermatitis Atópica/epidemiología , Ácidos Grasos Monoinsaturados , Femenino , Finlandia , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Inmunización , Masculino , Prevalencia , Aceite de Brassica napusRESUMEN
Lupin, a legume with good nutritional value, is used in food production today, most often in bakery products. In Finland, lupin is a labelled ingredient in very few products. Clinically relevant lupin allergy, even anaphylaxis, often occurs in patients without atopic background or other food allergies, whereas lupin sensitization without clinical relevancy most commonly seems to represent cross reactivity to other legumes. Lupin allergy should be suspected and studied in patients with adverse reactions to food, and patients with allergy to other legumes should be advised about possible lupin allergy, as well.
Asunto(s)
Hipersensibilidad a los Alimentos/inmunología , Lupinus/inmunología , HumanosRESUMEN
BACKGROUND: Allergen-mediated cross-linking of IgE antibodies bound to the FcepsilonRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking. METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release. CONCLUSIONS/SIGNIFICANCE: The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.
Asunto(s)
Alérgenos/química , Alérgenos/inmunología , Multimerización de Proteína , Alérgenos/genética , Animales , Antígenos Fúngicos , Antígenos de Plantas/química , Antígenos de Plantas/inmunología , Basófilos/inmunología , Bovinos , Cristalización , Cristalografía por Rayos X , Liberación de Histamina , Humanos , Espectrometría de Masas/métodos , Modelos Moleculares , Mutación , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Estructura Cuaternaria de ProteínaRESUMEN
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.
Asunto(s)
Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad Respiratoria/diagnóstico , Adolescente , Adulto , Angioedema , Antígenos de Plantas/inmunología , Niño , Reacciones Cruzadas , Disnea , Femenino , Finlandia , Harina/efectos adversos , Harina/análisis , Contaminación de Alimentos/análisis , Hipersensibilidad a los Alimentos/sangre , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/fisiopatología , Humanos , Inmunización , Inmunoglobulina E/sangre , Incidencia , Lupinus/efectos adversos , Lupinus/química , Masculino , Persona de Mediana Edad , Exposición Profesional , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/epidemiología , Hipersensibilidad Respiratoria/fisiopatología , Pruebas CutáneasRESUMEN
Cow's milk allergy (CMA) is a common food allergy, especially among infants and young children. Approximately 85% of milk-allergic children outgrow their allergy by the age of three but the remaining 15% remain allergic. Bovine beta-lactoglobulin (BLG) is one of the major allergens in cow's milk. There is a definite need for the specific and sensitive detection of allergenic substances. Validated methods are obligatory to demonstrate allergen contamination and even fatal hidden allergens and, thus, to prevent life-threatening conditions of allergic persons. In this study, we constructed human IgE scFv libraries from an adult milk-allergic patient and isolated the first recombinant IgE antibodies specific to a food allergen, BLG. The selection of the IgE antibody libraries with two distinct panning procedures resulted in the enrichment of four clones having different BLG-binding profiles; two of the clones recognize the native BLG whereas the other two recognize only the heat-denatured form of BLG. For further characterization, the scFv fragments were converted to Fab fragments with human IgG1 isotype. The D1 Fab fragment, binding native BLG with nanomolar affinity, also partially inhibited serum IgE binding to BLG. These BLG-specific IgE antibodies can be applied for the detection of both native and denatured BLG in cow's milk products and furthermore, for the optimization of manufacturing processes to develop safe hypoallergenic milk products.
Asunto(s)
Alérgenos/química , Anticuerpos Monoclonales/química , Clonación Molecular/métodos , Biblioteca de Genes , Inmunoglobulina E/química , Lactoglobulinas/química , Pliegue de Proteína , Adulto , Alérgenos/análisis , Alérgenos/inmunología , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Bovinos , Niño , Preescolar , Análisis de los Alimentos/métodos , Humanos , Inmunoglobulina E/genética , Inmunoglobulina E/inmunología , Lactoglobulinas/análisis , Lactoglobulinas/inmunología , Hipersensibilidad a la Leche/inmunología , Hipersensibilidad a la Leche/prevención & control , Conformación Proteica , Desnaturalización ProteicaRESUMEN
BACKGROUND: : No data have been available on severe allergic reactions in Finland. MATERIALS AND METHODS: : We summarize the data accumulated from 2000 to 2007 in the national register established at the Skin and Allergy Hospital of the Helsinki University Central Hospital, where physicians voluntarily report on patients with severe allergic reactions. RESULTS: : During the period, the 530 reported cases of severe allergic reactions represented an annual frequency of 0.001%. Of the patients, 66% were adults and 56% were female, with a median age of 27 years. Food was the causative agent in 53% of the cases, drugs in 26%, allergen preparations in 12%, and insects in 8%. Dermatologic symptoms were reported in 85%, respiratory in 76%, cardiovascular in 50%, gastrointestinal in 33%, and eye/nose symptoms in 18%. The reaction was a life-threatening anaphylactic shock in 26% of the cases, with no deaths reported. Patients were treated with intramuscular adrenaline in 75% of the cases. Not only nuts and seeds, but also fruit and vegetables were the most important allergens for the adults. Nuts were also important allergens for children, along with milk, egg, and wheat. In addition, many "exotic" allergens were identified: patent blue, carmine dye, yeast, buckwheat, and macrogol. CONCLUSIONS: : Severe allergic reactions are underreported, but a register reflects the real-life situation and helps to identify new causative agents. It also contributes to improvements in first aid treatment practice.
RESUMEN
Allergies are caused by the immune reaction to commonly harmless proteins, allergens. This reaction is typified by immunoglobulin E (IgE) antibodies. We report the crystal structure of an IgE Fab fragment in complex with beta-lactoglobulin (BLG), one of the major allergens of bovine milk. The solved structure shows how two IgE/Fab molecules bind the dimeric BLG. The epitope of BLG consists of six different short fragments of the polypeptide chain, which are located especially in the beta strands, covering a flat area on the allergen surface. All six CDR (complementary-determining region) loops of the IgE Fab participate in the binding of BLG. The light chain CDR loops are responsible for the binding of the flat beta sheet region of BLG. The IgE epitope is different from common IgG epitopes that are normally located in the exposed loop regions of antigens and observed also in the two recently determined allergen-IgG complexes.
Asunto(s)
Alérgenos/química , Inmunoglobulina E/química , Lactoglobulinas/química , Lactoglobulinas/inmunología , Alérgenos/inmunología , Secuencia de Aminoácidos , Animales , Bovinos , Cristalografía por Rayos X , Epítopos/química , Epítopos/inmunología , Inmunoglobulina E/inmunología , Datos de Secuencia Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunologíaRESUMEN
Enzymes are high-molecular-weight proteins and highly sensitizing occupational allergens used widely in industrial processes. Lactase has been described to cause work-related respiratory and conjunctival immunoglobulin (Ig)-E-mediated sensitizations in workers in the pharmaceutical industry. In these previous reports, allergic rhinoconjunctivitis or asthma was confirmed with prick tests but not by challenge tests. Lactase previously has not been described as a cause of immediate or delayed contact skin reaction. Furthermore, there are no previous reports of lactase-specific IgE. We report a case of protein contact dermatitis and allergic rhinoconjunctivitis from occupational exposure to lactase in a pharmaceutical worker. The patient exhibited strong positive responses to lactase in prick tests. In an open application test, lactase elicited whealing, and in patch testing, lactase elicited an eczematous reaction. Serum lactase-specific IgE antibodies were demonstrated in immunospot and radioallergosorbent test assays, and lactase-IgE-binding fractions and their specificities were examined in immunoblot and immunoblot inhibition assays. The chamber challenge test was performed to detect the association between lactase sensitization and rhinoconjunctival symptoms. Our results have confirmed the previous observations that lactase can induce occupational IgE-mediated respiratory and conjunctival sensitizations, but they show that contact skin reactions caused by lactase may also occur.
Asunto(s)
Alérgenos/efectos adversos , Conjuntivitis Alérgica/diagnóstico , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Profesional/diagnóstico , Lactasa/efectos adversos , Adulto , Alérgenos/inmunología , Conjuntivitis Alérgica/sangre , Conjuntivitis Alérgica/etiología , Conjuntivitis Alérgica/patología , Dermatitis Alérgica por Contacto/sangre , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/patología , Dermatitis Profesional/sangre , Dermatitis Profesional/etiología , Dermatitis Profesional/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina E/inmunología , Lactasa/inmunología , Servicios Farmacéuticos , Pruebas de Función Respiratoria , Pruebas CutáneasRESUMEN
BACKGROUND: Respiratory allergy to environmental molds is relatively common, and fungal allergen-specific reactivity seems to cluster in certain persons. However, generalized reactions caused by ingested fungi have seldom been described. OBJECTIVE: To describe a mold-sensitized patient who developed multiple anaphylactic reactions after ingesting a yeast preparation widely used by the food industry as flavoring in, for example, powdered and ready-made sauces. METHODS: Skin prick tests and serum IgE tests were performed with inhalant and food allergens, including molds and yeasts, 2 pasta sauces consumed by the patient, individual sauce ingredients, and a food-quality yeast extract. Radioallergosorbent test inhibition was used for specificity studies. RESULTS: Skin prick and serum IgE test results were positive to several molds (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, and Penicillium notatum), baker's yeast (Saccharomyces cerevisiae), Malassezia furfur, and champignon and to the 2 pasta sauces, the yeast ingredient, and a food-quality yeast extract. Radioallergosorbent test inhibition studies confirmed that the sauces contain cross-reacting yeast and mold allergens. CONCLUSIONS: This patient has a clustered sensitization to fungi characterized by allergy to environmental fungal allergens and to yeast extracts used in the food industry. Yeasts should be considered as possible ingestive allergens in mold-allergic patients.
Asunto(s)
Anafilaxia/microbiología , Hipersensibilidad a los Alimentos/microbiología , Hongos/inmunología , Adulto , Anafilaxia/inmunología , Asma/inmunología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Immunoblotting , Inmunoglobulina E/sangre , Prueba de Radioalergoadsorción , Pruebas CutáneasRESUMEN
There are numerous reports of anaphylaxis from chlorhexidine in surgical operations and other medical procedures, usually due to its application to wounds or mucous membranes. We wanted to analyse the clinical data of patients with a positive chlorhexidine prick test and perform some additional testing. We studied the case records of the patients with a positive chlorhexidine prick test and performed an open application test and tests for specific IgE. We found 33 patients with a positive prick test. 10 of them had had severe symptoms from chlorhexidine, and 11 had had only mild local symptoms. The size of the prick test reaction was mainly in line with the strength of the severest symptoms. Small 3- to 4-mm reactions were usually without obvious clinical relevance. Specific IgE could be demonstrated in 6 patients out of 14 tested by the ImmunoCAP method. Besides severe attacks, patients with a positive prick test often have milder local symptoms, such as exacerbation of dermatitis. Local symptoms from chlorhexidine-containing products may precede severe attacks. We recommend a prick test to be performed routinely when symptoms during medical interventional procedures, e.g. local and general anaesthesia, are investigated.
Asunto(s)
Alérgenos/efectos adversos , Clorhexidina/efectos adversos , Dermatitis Alérgica por Contacto/epidemiología , Hipersensibilidad Inmediata/epidemiología , Adolescente , Adulto , Anciano , Alérgenos/inmunología , Niño , Clorhexidina/inmunología , Dermatitis Alérgica por Contacto/sangre , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/patología , Femenino , Finlandia/epidemiología , Hospitales Universitarios , Humanos , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/etiología , Hipersensibilidad Inmediata/patología , Inmunoglobulina E/inmunología , Lactante , Masculino , Registros Médicos , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas CutáneasRESUMEN
BACKGROUND: Patients sensitized to airborne fungi such as Alternaria alternata and Cladosporium herbarum often also show positive skin prick test results and specific serum IgE antibodies to a yeast, Pityrosporum ovale. We examined whether part of the IgE binding to these fungi is explained by cross-reacting mould and yeast allergens. METHODS: Serum samples from 36 patients with positive skin prick test to A. alternata or C. herbarum were analyzed for IgE antibodies to fungal extracts by ELISA and immunoblot analysis. Cross-reactivity between mould and yeast extracts was studied by ELISA and immunoblot inhibition assays. In further analysis, the mannan-containing glycoproteins were removed from the yeast extract by concanavalin A-Sepharose chromatography, and the IgE binding properties of the extracts were compared. RESULTS: Serum IgE reactivity to P. ovale was found in 40% of the mould-sensitized patients. The IgE antibody binding to A. alternata and C. herbarum moulds was partially inhibited by the yeast P. ovale in ELISA and immunoblot inhibition assays. When the glycoproteins were removed from the extract, cross-reactivity was markedly reduced. CONCLUSION: Part of the IgE binding to mould and yeast allergen extracts is due to cross-reacting glycoproteins. False-positive IgE and skin prick test results should be taken into account in the diagnosis of mould allergy.
Asunto(s)
Alérgenos/inmunología , Cladosporium/inmunología , Proteínas Fúngicas/inmunología , Glicoproteínas/inmunología , Malassezia/inmunología , Alérgenos/metabolismo , Antígenos Fúngicos/inmunología , Antígenos Fúngicos/metabolismo , Sitios de Unión de Anticuerpos , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Proteínas Fúngicas/metabolismo , Glicoproteínas/metabolismo , Humanos , Inmunoglobulina E/metabolismoRESUMEN
Shiitake are popular edible mushrooms all over the world, and eating raw shiitake may lead to relatively common 'shiitake dermatitis' or toxicodermia. Workers involved in shiitake cultivation and marketing have distinct occupational respiratory and skin diseases unrelated to 'shiitake dermatitis'. There are no previous reports of protein contact dermatitis (PCD) from shiitake, and there is only 1 report of shiitake-specific immunoglobulin (Ig) E. We report 2 shiitake growers who developed work-related eczematous eruption on their hands. Both of the patients had small prick test reactions to fresh shiitake, and specific IgE to shiitake was detected in their sera by immunospot. One of the patients had a large prick test reaction to dry shiitake and also a positive wheal reaction to fresh shiitake in an open application test. Neither of the patients had noticed any symptoms of contact urticaria at work. Both of the patients had immediate IgE-mediated allergy to shiitake, and the diagnosis of occupational PCD was made. There are no commercial in vitro tests for shiitake-specific IgE. Tests for immediate allergy are important when shiitake contact dermatitis is investigated.
Asunto(s)
Dermatitis Profesional/etiología , Proteínas Fúngicas/efectos adversos , Inmunoglobulina E/sangre , Hongos Shiitake/inmunología , Adulto , Dermatitis Profesional/diagnóstico , Dermatitis Profesional/inmunología , Femenino , Manipulación de Alimentos , Proteínas Fúngicas/inmunología , Humanos , Persona de Mediana Edad , Pruebas CutáneasRESUMEN
BACKGROUND: Deer keds (elk fly) have not previously been described as a cause of respiratory or conjunctival sensitization. OBJECTIVE: To report a case of IgE-mediated allergic rhinoconjunctivitis from occupational exposure to deer ked. METHODS: Skin prick testing (SPT) was performed with pollens, animal danders, mites, molds, and deer ked. The serum deer ked-specific IgE level was examined in ImmunoSpot and radioallergosorbent test assays, and deer ked IgE-binding fractions and their specificities were examined in immunoblot and immunoblot inhibition assays. Nasal provocation testing (NPT) and conjunctival provocation testing (CPT) were performed to detect the association between deer ked sensitization and rhinoconjunctival symptoms. Both SPT and NPT were performed with deer ked whole-body extract, whereas CPT was performed with deer ked wing. RESULTS: The results of SPT, NPT, and CPT were positive for deer ked. In laboratory tests, serum deer ked-specific IgE antibodies were demonstrated in radioallergosorbent test and ImmunoSpot assays. In immunoblot, IgE-binding bands were demonstrated at 17, 33, 70, and 85 kDa, which were clearly inhibited with deer ked extract but not with the control extract. CONCLUSIONS: Occupational IgE-mediated rhinoconjunctival allergy to deer ked was confirmed in this patient.