IgE-Mediated Sensitization to Galactose-α-1,3- Galactose (α-Gal) in Urticaria and Anaphylaxis in Spain: Geographical Variations and Risk Factors.

BACKGROUND: The objectives of this study were to investigate the prevalence of sIgE to galactose-α-1,3-galactose (α-gal) in individuals with acute urticaria or anaphylaxis from different geographical areas of Spain and to evaluate the relevance of demographics and lifestyle as risk factors for this immune response. METHODS: Participants were recruited from allergy departments at 14 Spanish hospitals. Patients aged 18 years or older presenting with urticaria or anaphylaxis were enrolled into one of 2 arms: cases and controls. An interviewer-administered questionnaire collecting demographic data, lifestyle habits, and the presence of cofactors was obtained from each participant. sIgE to α-gal and total IgE were determined using ImmunoCAP. sIgE levels ≥0.35 kU/L were considered a positive result. RESULTS: The study population comprised 160 cases and 126 controls. The median age was 44 years. The overall prevalence of a positive result of sIgE to α-gal was 15.7%; this was higher in cases (26.3%) than in controls (2.4%). The sIgE anti-α-gal positivity rate ranged from 37.68% (rural) to 15.38% (semiurban), and 7.85% (urban). The rates of positivity were 46.32%, (Northern), 0.72% (Center), and 0% (Mediterranean). A positive result for sIgE to α-gal was associated with a history of tick bites, participation in outdoor activities, pet ownership, and ingestion of mammalian meats or innards before the onset of symptoms. Only alcohol consumption could be implicated as a cofactor. CONCLUSION: Sensitization to α-gal in patients with urticaria or anaphylaxis differs considerably between the 3 geographical areas studied and is related to tick bites.

Tomato nsLTP as an "In Vivo" Diagnostic Tool: Sensitization in a Mediterranean Population.

BACKGROUND: Tomato allergies have been extensively studied but component-resolved in vivo diagnosis with purified allergens has yet to be performed. OBJECTIVES: To evaluate the prevalence of sensitization to Sola l 3 in a Mediterranean population, and to compare the resulting sensitization profile with that of individuals sensitized to tomato, peach, and/or purified lipid transfer protein (LTP). METHODS: Sola l 3 was purified, characterized, and used to prepare skin prick tests (SPTs). Two groups of patients were selected. Group 1 consisted of patients with at least 1 positive SPT to tomato, peach, or LTP mixture (marker extracts) who were subsequently tested with Sola l 3 (n = 280). Group 2 (prevalence study) consisted of patients who underwent simultaneous SPT with the 3 marker extracts and Sola l 3 (n = 658). Patients from either group who were positive to any of the 4 extracts were studied in detail (study group, n = 1 23). ELISA and immunoblot assays were performed in individuals with a positive SPT to Sola l 3 to detect the presence of specific IgE antibodies to this allergen. RESULTS: Prevalence of sensitization to Sola l 3 was 3.2% overall and 54.7% in tomato-positive patients. Most tomato-sensitized patients were asymptomatic. Symptoms were more common in Sola l 3-positive individuals. Sensitization to peach and the LTP mixture did not discriminate between Sola l 3-positive and Sola l 3-negative patients. CONCLUSIONS: This study confirms that LTP, not only from peach but also from other fruit and vegetables, including tomato, is an important allergen in the Mediterranean area. Sensitization to Sola l 3 is associated with more symptoms in tomato-sensitized patients.

Goji berries (Lycium barbarum): risk of allergic reactions in individuals with food allergy.

BACKGROUND: New foods are frequently introduced in Western diets for their healthy properties; however, they may produce adverse effects. OBJECTIVE: After attending a patient who experienced an allergic reaction to Goji berries, we evaluated the allergenic potential of this food in plant food-allergic individuals, a group that is considered to be at high risk of experiencing a reaction. METHODS: We recruited 30 additional plant food-allergic individuals in Spain during 3 months in 2010. Four patients reported symptoms on intake, 6 tolerated the berries, and 20 had never tried Goji berries. Patients underwent skin prick tests with Goji berries, as well as with peach peel and plant food panallergens as markers of cross-reactivity between unrelated foods. We carried out in vitro tests in symptomatic patients. RESULTS: Skin tests to Goji berries were positive in 24 patients (77%): 5 symptomatic patients and 19 asymptomatic patients. Positivity to Goji berries was associated with positivity to peach peel and to the panallergen nonspecific lipid transfer protein (LTP). Nearly half of the patients reported symptoms (45%), but 89% of the skin test-positive patients had never eaten Goji berries. We detected specific immunoglobulin E to Goji berries in all cases, and several individuals recognized 2 protein bands in the immunoblot. Addition of LTP to sera mostly inhibited immunoglobulin E binding to an LTP-like band, suggesting a role for this panallergen in sensitization to Goji berries. CONCLUSIONS: Our results demonstrate the allergenic potential of Goji berries in high-risk individuals, which is probably due to cross-reactivity with LTP from other foods. The risks of Goji berries should be taken into consideration in individuals with food allergy, especially those who are allergic to LTP.

Acidic ribosomal protein 60S: A new tomato allergen.

Three tomato allergens (Lyc e 1, Lyc e 2 and Lyc e 3) have been characterised until now. Previous studies have demonstrated the existence of other proteins with capacity to bind IgE. The objective of this study was to identify new tomato allergens by molecular biology techniques. A tomato peel cDNA library was screened using a specific pool of sera from sensitised individuals. A clone was obtained and its sequence compared to other described allergens. This clone contained 34 aminoacids from the C-terminal region of an acidic ribosomal protein 60S. This protein showed more than 85% of homology with fungal allergens and 93.8% of homology with the almond allergen Pru du 5. The clone also contains 169 base pairs without homology with other known genes and could correspond to non-coding sequences. The IgE detection with a pool of sera was positive which confirms that is a new tomato allergen.

Allergenic differences among pollens of three Salsola species.

BACKGROUND: Sensitivity to Chenopodiaceae is a frequent cause of allergic respiratory diseases in geographic areas where sensitization to Salsola kali and Chenopodium album has been reported. The objective of this study was to evaluate the pattern of sensitization to 3 Salsola species in patients residing on the Mediterranean coast of south-eastern Spain. METHODS: S. kali, S. vermiculata and S. oppositifolia pollen extracts were prepared. Patients reporting respiratory and/or cutaneous symptoms were skin prick tested with the 3 Salsola extracts. Individuals with positive skin prick tests to at least 1 of the 3 Salsola species were included. Specific IgE was determined by direct ELISA. SDS-PAGE and 2-D analysis were conducted to elucidate the protein profile. The allergenic profile was investigated by immunoblot. Inhibition experiments were conducted to establish cross-reactivity between different species. RESULTS: 246 patients were included. 237 patients (96.3%) tested positive to S. oppositifolia, 189 (76.8%) to S. kali and 185 (75.2%) to S. vermiculata. Protein profile and immunoblot demonstrated similar patterns in all extracts, except in low-molecular-weight allergens of S. oppositifolia. Immunoblot inhibition experiments demonstrated that most high-molecular-weight allergens of S. oppositifolia were inhibited by S. kali whereas low-molecular-weight allergens were totally inhibited only by C. album. CONCLUSIONS: This study confirms the allergenic importance of other Salsola species, especially S. oppositifolia. We have demonstrated that the 3 species show a high degree of cross-reactivity, but S. oppositifolia shares more allergenic similarities with C. album than S. kali.

Sensitization to tomato peel and pulp extracts in the Mediterranean Coast of Spain: prevalence and co-sensitization with aeroallergens.

BACKGROUND: Tomatoes (Lycopersicon esculentum) are consumed world-wide. The prevalence of sensitization to tomatoes remains unknown. OBJECTIVE: To determine the prevalence of skin test reactivity to tomato and to describe the characteristics of tomato-sensitized subjects. METHODS: Individuals attending for the first time during the period of the study to six Allergy centres, located along the Mediterranean coast of Spain, reporting respiratory and/or cutaneous symptoms, were included. All patients were skin prick tested with a battery of inhalant allergens and with peel and pulp of Canary tomato extracts. RESULTS: The study included 1734 individuals (757 males, 977 females; 31.9+/-17.8 years old). The prevalence of sensitization to tomato was 6.52% (113 patients; 65 males, 48 females; 29.5+/-13 years old). The peel extract was positive in 110 patients and the pulp extract in 47 patients; three patients were positive exclusively to pulp. Only 1.8% of individuals reported symptoms with tomato; 44% of them had skin test negative to both extracts. Among tomato-sensitized subjects, 16% reported symptoms with tomato, 97% were sensitized to inhalant aeroallergens, including 84% to pollens (mainly Artemisia vulgaris and Platanus hybrida), with differences between Northern and Southern centres. CONCLUSIONS: The prevalence found of skin test sensitivity to tomato is high. Peel extracts detected most of the sensitized subjects. Most of the sensitized subjects were asymptomatic and some patients reported symptoms without skin test sensitivity. Positive subjects were very frequently sensitized to pollens, suggesting allergen cross-reactivity. Regional differences may exist, possibly related to the pattern of sensitization to cross-reacting pollens.

Estudio coste-efectividad de la aplicación del diagnóstico genético en la valoración de la enfermedad celíaca / Cost-effectiveness study of using genetic diagnosis in evaluation of celiac disease

La enfermedad celíaca (EC) se desarrolla exclusivamente enindividuos genéticamente predispuestos. El objetivo de esteestudio es valorar la utilidad de la determinación del HLADQ2en el despistaje de la EC en población de riesgo. Se hanestudiado un total de 682 individuos: 174 niños celíacos,191 familiares de primer grado de pacientes celíacos, 83niños con diabetes mellitus tipo I, 64 niños con diagnósticodudoso de EC y 164 controles. El HLA-DQ2 positivo lo presentanel 34,7% de los controles, el 96% de la población decelíacos, el 66% de sus familiares de primer grado y el72,2% de los niños diabéticos. El 51,5% de los pacientescon sospecha de enfermedad celíaca y diagnóstico no concluyenteeran HLA-DQ2 positivos y, en este grupo, todos losniños con anticuerpos antiendomisio positivos portaban elHLA-DQ2 aunque en ellos no se confirmara la EC. La caracterizacióngenética de los familiares de los niños celíacos descartala enfermedad en un 34%, no siendo necesario en ellosseguimiento serológico a largo plazo. La elevada prevalenciadel HLA-DQ2 en los niños diabéticos y en pacientes con serologíapositiva de EC y diagnóstico dudoso hace que el estudiogenético sea de escasa utilidad en el despistaje de la EC

Celiac Disease (CD) is developed in only genetically susceptibleindividuals. The aim of this study is to investigatewhether HLA-DQ2 typing is helpful in exclusion of CD inpatients at risk of developing CD. 682 individuals havebeen tested: 174 children with CD, 191 of first degreerelatives of celiac children, 83 children with type 1 diabetes,64 with CD uncertain diagnosis and 164 controls.HLA-DQ2 haplotype was present in 34,7% of controls,96% of celiac children, 66% of relatives, 72,2% of diabeticchildren and 51,5% of children with uncertain diagnosisof CD. In this group, all endomysial antibodies positivepatients with non confirmed CD were HLA-DQ2 positive.HLA-DQ2 typing in first-degree relatives of celiac patientscould eliminate 34% of the population from needing serialautoantibody testing. HLA-DQ2 typing in children with type1 diabetes and children with positive serology and uncertaindiagnosis of CD is not useful because of the high prevalenceof HLA-DQ2 positivity in these study groups

Propuesta para una clasificación de la alergia a los alimentos / Proposal for a classification of food allergy

Introducción: Aunque parece que el interés por la alergia a los alimentos ha crecido en los últimos años y que cada vez se diagnostican más pacientes adultos, la mayoría de los conceptos se basan en la alergia a los alimentos que se ven en los niños. Se propone una clasificación de la alergia a los alimentos mediada por IgE basada tanto en la capacidad de los alimentos para inducir síntomas, en la susceptibilidad de los sujetos para reaccionar a ellos y en sus posibles variaciones con la edad. Clasificación: 1. Alergia a los alimentos independiente: el alimento es necesario y suficiente por sí mismo para desencadenar una reacción alérgica en los sujetos sensibilizados. 1. 1. Alergia a los ali-mentos primaria: los alergenos son capaces de sensibilizar a sujetos predispuestos (alergenos completos). 1. 1. 1. Alergia a los alimentos de la infancia: "alergia a los alimentos clásica". Probablemente la inmadurez (tanto del aparato digestivo como del sistema inmunitario) favorecen la sensibilización en los primeros contactos con el alimento. 1. 1. 2. Alergia a los alimentos del adulto: pacientes monosensibilizados que comienzan a tener síntomas en la edad adulta. De existir estos pacientes, la patogenia estaría sin aclarar. 1. 2. Alergia a los alimentos secundaria: los alergenos alimentarios responsables no son capaces de sensibilizar a través del aparato digestivo (alergenos incompletos). Los síntomas ocurrirían en pacientes sensibilizados antes por vía respiratoria, cutánea, etc. Incluye el síndrome de la alergia oral, pero también síntomas sistémicos, y podría deberse a la reactividad cruzada existente entre los alergenos. 2. Alergia a los alimentos dependiente: el alimento es necesario pero no suficiente para desencadenar una reacción clínica en los sujetos sensibilizados. Los alergenos alimentarios podrían en este caso estar "excluidos" o ser incapaces de contactar con el sistema inmunitario (alergenos excluidos o protegidos). Sería necesario algún factor adicional para que ocurriera una reacción clínica. La alergia a los alimentos dependiente del ejercicio sería el modelo. También podrían ser importantes otros factores menos estudiados (fármacos, infecciones, etc). 3. Aler-gia relacionada con los alimentos: los alimentos están relacionados con la aparición de los síntomas pero no está claro si son necesarios, importantes o simplemente espectadores. Se trataría de un grupo observacional en el que poder situar temporalmente a los pacientes mientras se encuentra un diagnóstico definitivo. Los sujetos con alergia a Anisakis son un ejemplo de pacientes que debieran haber permanecido en este grupo. 4. Alergia a los alimentos por vía no digestiva: el alimento es capaz de producir síntomas por inhalación o contacto. Incluye tanto la alergia grave a los alimentos como las enfermedades ocupacionales provocadas por los alimentos (asma ocupacional, dermatitis proteínica,etc). Conclusiones: Esta propuesta intenta aumentar nuestra comprensión de la alergia a los alimentos incluyendo para ello a todos los pacientes con síntomas sugestivos de alergia a los alimentos mediada por IgE. También podría ayudar a interpretar algunas de las discordancias que a veces se observan entre la anamnesis y el estudio alergológico. Si la demostración de una relación causa-efecto entre un alimento y los síntomas es fundamental para confirmar el diagnóstico, su ausencia puede no ser suficiente para excluirlo (AU)

Comparative study of inhaled amiloride and inhaled furosemide in exercise-induced asthma.

BACKGROUND: Certain diuretics such as furosemide, when inhaled, have been found to be useful in preventing Exercise-Induced Asthma (EIA). STUDY OBJECTIVE: To assess the possible preventive effect of inhaled amiloride in EIA. DESIGN: A double blind, randomized, cross-over study comparing the effect of inhaled amiloride, inhaled furosemide and placebo in EIA. PATIENTS: Sixteen asthmatic patients (8 males and 8 females) with an average age of 21 years (range 9-31) who presented a FEV1 decrease of over 15% in a previous free-running exercise test. INTERVENTIONS: Solutions were inhaled with a Hudson nebulizer connected to an oxygen source in different days before exercise testing. A Vitalograph Compact (Ohmeda, England) spirometer was used and FEV1 was obtained at baseline, three minutes after solution inhalation, immediately after exercise and then every 5 min. until 20 minutes post-exercise. The changes in FEV1 percentages (FEV1%) and the mean FEV1 decreases expressed as percentages for each solution were compared. RESULTS: Inhaled furosemide diminished the fall in the FEV1 at every time after exercise. The maximum decrease in mean FEV1 was at 5 minutes post-exercise and was 11 +/- 7% with furosemide, 24 +/- 14% (p < 0.01) with amiloride and 19 +/- 12% (p < 0.05) with placebo. Amiloride administration resulted in a slight but significative increase in the FEV1 fall (p < 0.01 when compared with placebo). CONCLUSIONS: Amiloride is not useful to protect EIA whereas Furosemide does it. These differences results may be related to the differents mechanisms of action of the two diuretics.

Endobronchial tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the presence of endobronchial tuberculosis in HIV-infected patients. METHODS: Review of the clinical records of HIV-infected patients in whom diagnostic bronchoscopy was performed because of pulmonary signs or symptoms during a 3-year period. RESULTS: Seventy bronchoscopies were performed in 59 HIV-infected patients. tuberculosis was diagnosed in 25 patients, of whom six showed endobronchial tuberculosis. The most noteworthy radiological finding was mediastinal and/or hilar lymphadenopathy in five patients, occasionally associated with chest miliary infiltrates (in one), or a small pleural effusion (in two). Chest radiograph was normal in one case. The endoscopic findings were hyperaemia in five, caseating bronchial masses in four, or protrusion of extratracheal lymph nodes (broad, thickened carina and patchy bronchial lesions) in three out of the six patients. Mycobacterium tuberculosis infection was confirmed by smear and culture from bronchial aspirate, bronchoalveolar lavage or bronchial biopsies. In three cases the diagnosis was confirmed by transcarinal needle mediastinal puncture aspiration. Tuberculosis was the first opportunistic pulmonary infection in every case. The clinical course with standard treatment was satisfactory in all cases with no bronchial sequelae. CONCLUSION: Endobronchial tuberculosis may be more frequent than suspected in HIV-infected patients. Routine fibrobronchoscopy in HIV-positive patients with tuberculosis could show the true frequency of endobronchial tuberculosis.

Possible consequences of elimination diets in asymptomatic immediate hypersensitivity to fish.

The natural history of IgE antibodies to food without related symptoms is unknown. We have followed the progress of 7 children with various atopic diseases and asymptomatic immediate hypersensitivity to fish, treated with elimination diet in spite of full alimentary tolerance. During the diet period, between 24 and 113 months, all 7 patients presented immediate symptoms upon accidental exposure to or challenge tests with fish (skin symptoms in all 7 cases, digestive in 5, respiratory in 4, and anaphylaxis in 2), which differed from those related to atopic diseases previously present. The levels of fish-specific IgE (prick test, RAST) remained unchanged or were increased. These findings suggest that during elimination diet, and perhaps due to minimal and hidden contact with the allergen, the patients' degree of sensitization may increase, turning an asymptomatic into a symptomatic immediate hypersensitivity.