Low Expression of ICAM-1 in Blood Eosinophils in Patients With Active Eosinophilic Esophagitis.

BACKGROUND AND OBJECTIVE: Eosinophilic esophagitis (EoE) is a chronic and isolated inflammation of the esophagus characterized by a marked infiltration of eosinophilic leukocytes. Diagnosis and course of the disease are based exclusively on histopathology. Therefore, patients must undergo several esophageal biopsies, implying a risk associated with the procedure and considerable use of resources. Objective: The presence of active circulating eosinophils, which are quantifiable through the expression of specific cellular activation proteins in their membrane, could be consistent with histopathological findings, which are currently the only valid parameters in studies on EoE. METHODS: The activity of peripheral blood eosinophils from patients with EoE was analyzed by identifying 5 surface molecules (CD69, IL- 5Rα, CD44, ICAM-1, CD63), which are seen to be expressed by the active eosinophils in flow cytometry. The results were compared with the infiltrate of eosinophils present in patients' esophageal biopsies. RESULTS: ICAM-1 levels decreased significantly in patients with active EoE compared with nonactive EoE patients, allergic patients, and healthy controls. In patients with EoE, an inverse correlation was observed between the number of eosinophils in the esophageal biopsy and the percentage of ICAM-1 expression in peripheral blood eosinophils. No differences were observed for the remaining molecules studied. CONCLUSION: Expression of ICAM-1 in blood eosinophils could be a useful noninvasive marker for the diagnosis and assessment of patients with EoE.

Low Expression of ICAM-1 in Blood Eosinophils in Patients With Active Eosinophilic Esophagitis

Background: Eosinophilic esophagitis (EoE) is a chronic and isolated inflammation of the esophagus characterized by a marked infiltration of eosinophilic leukocytes. Diagnosis and course of the disease are based exclusively on histopathology. Therefore, patients must undergo several esophageal biopsies, implying a risk associated with the procedure and considerable use of resources. Objective: The presence of active circulating eosinophils, which are quantifiable through the expression of specific cellular activation proteins in their membrane, could be consistent with histopathological findings, which are currently the only valid parameters in studies on EoE. Methods: The activity of peripheral blood eosinophils from patients with EoE was analyzed by identifying 5 surface molecules (CD69, IL- 5Rα, CD44, ICAM-1, CD63), which are seen to be expressed by the active eosinophils in flow cytometry. The results were compared with the infiltrate of eosinophils present in patients’ esophageal biopsies. Results: ICAM-1 levels decreased significantly in patients with active EoE compared with nonactive EoE patients, allergic patients, and healthy controls. In patients with EoE, an inverse correlation was observed between the number of eosinophils in the esophageal biopsy and the percentage of ICAM-1 expression in peripheral blood eosinophils. No differences were observed for the remaining molecules studied. Conclusion: Expression of ICAM-1 in blood eosinophils could be a useful noninvasive marker for the diagnosis and assessment of patients with EoE (AU)

The method for selecting basophils might be determinant in the basophil activation test in patients with mastocytosis

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Seasonal Local Allergic Rhinitis in Areas With High Concentrations of Grass Pollen.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. OBJECTIVE: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. METHODS: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. RESULTS: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. CONCLUSIONS: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Is Microarray Analysis Really Useful and Sufficient to Diagnose Nut Allergy in the Mediterranean Area?

BACKGROUND: Component-based diagnosis on multiplex platforms is widely used in food allergy but its clinical performance has not been evaluated in nut allergy. OBJECTIVE: To assess the diagnostic performance of a commercial protein microarray in the determination of specific IgE (sIgE) in peanut, hazelnut, and walnut allergy. METHODS: sIgE was measured in 36 peanut-allergic, 36 hazelnut-allergic, and 44 walnut-allergic patients by ISAC 112, and subsequently, sIgE against available components was determined by ImmunoCAP in patients with negative ISAC results. ImmunoCAP was also used to measure sIgE to Ara h 9, Cora 8, and Jug r 3 in a subgroup of lipid transfer protein (LTP)-sensitized nut-allergic patients (positive skin prick test to LTP-enriched extract). sIgE levels by ImmunoCAP were compared with ISAC ranges. RESULTS: Most peanut-, hazelnut-, and walnut-allergic patients were sensitized to the corresponding nut LTP (Ara h 9, 66.7%; Cor a 8, 80.5%; Jug r 3, 84% respectively). However, ISAC did not detect sIgE in 33.3% of peanut-allergic patients, 13.9% of hazelnut-allergic patients, or 13.6% of walnut-allergic patients. sIgE determination by ImmunoCAP detected sensitization to Ara h 9, Cor a 8, and Jug r 3 in, respectively, 61.5% of peanut-allergic patients, 60% of hazelnut-allergic patients, and 88.3% of walnut-allergic patients with negative ISAC results. In the subgroup of peach LTP-sensitized patients, Ara h 9 sIgE was detected in more cases by ImmunoCAP than by ISAC (94.4% vs 72.2%, P < .05). Similar rates of Cora 8 and Jug r 3 sensitization were detected by both techniques. CONCLUSIONS: The diagnostic performance of ISAC was adequate for hazelnut and walnut allergy but not for peanut allergy. sIgE sensitivity against Ara h 9 in ISAC needs to be improved.

Seasonal local allergic rhinitis in areas with high concentrations of grass pollen

Background: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. Objective: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. Methods: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. Results: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. Conclusions: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis (AU)

Introducción: La rinitis alérgica local (RAL) es un fenotipo de rinitis alérgica (RA) caracterizado por la presencia de una respuesta inmunológica localizada en la mucosa nasal de pacientes con pruebas cutáneas (PC) negativas e IgE específica (sIgE) sérica no detectable. Se desconoce si la RAL es una entidad limitada a áreas con baja o moderada exposición a aeroalérgenos. Objetivos: Explorar la presencia y características clínico-inmunológicas de la RAL en áreas geográficas con alta concentración atmosférica de polen de gramíneas. Métodos: Estudio observacional-transversal realizado en dos hospitales de la zona centro de España (Madrid y Ciudad Real). Sesenta y un pacientes con rinitis estacional, PC negativas y sIgE sérica no detectable fueron evaluados mediante cuestionario clínico, IgE total sérica, y test de provocación nasal con Phleum (TPN-Phleum). La respuesta al TPN se monitorizó mediante síntomas, rinometría acústica, y determinación de sIgE, triptasa y proteína catiónica de eosinófilos en secreciones nasales. Resultados: Se detectó RAL estacional en 37 pacientes (61%) mediante TPN-Phleum. El 11% de los pacientes eran adolescentes o niños, y el 14% habían comenzado con los síntomas en la infancia. La mayoría presentaban rinitis estacional persistente-moderada, y el 41% refirió empeoramiento en los 2 últimos años. La conjuntivitis fue la enfermedad asociada más frecuente, afectando al 95% de los sujetos con RAL. Conclusiones: La RAL por polen de gramíneas es una enfermedad frecuente en pacientes con síntomas indicativos de RA estacional y PC negativas que viven en áreas con alta concentración atmosférica de pólenes, y debe ser incluida en el diagnostico diferencial de la rinitis (AU)

Is the ISAC 112 microarray useful in the diagnosis of pollinosis in Spain?

Background: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. Methods: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. Results: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. Conclusions: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap (AU)

Introducción: La sensibilización a múltiples pólenes es frecuente entre los pacientes alérgicos a polen. El objetivo de este estudio fue determinar la exactitud diagnóstica de la micromatriz ImmunoCAP ISAC 112 (ISAC112) en alergia a polen de diversos taxones y su utilidad clínica en una población española. Métodos: Se determinó IgE específica mediante ISAC112 en 390 pacientes polínicos. Se calculó su exactitud diagnóstica (sensibilidad, especificidad, valores predictivos y área bajo la curva ROC) para el diagnóstico de alergia a polen de gramíneas (n=49), ciprés (n=75), olivo (n=33), plátano de sombra (n=63) y parietaria (n=17) y se comparó con la de ImmunoCAP monocomponente (CAP). Resultados: La sensibilidad de ISAC112 osciló entre 68,2% para alergia a polen de plátano de sombra y 93,9% a polen de gramíneas. La especificidad se situó por encima del 90% en todos los casos. El área bajo la curva (AUC) de la curva ROC para diagnóstico de alergia a polen de plátano fue de 0,798. El resto de AUC fueron ≥ 0,876. La exactitud diagnóstica de ISAC112 fue superior a la de CAP para la alergia a polen de plátano de sombra y similar para el resto de pólenes estudiados. La frecuencia de sensibilización a la mayoría de componentes alergénicos genuinos y a profilinas varió entre las diferentes zonas. El 73 % de los pacientes polínicos estaban sensibilizados a componentes genuinos de más de un tipo polínico. Conclusiones: ISAC112 es una herramienta exacta para el diagnóstico de alergia al polen de gramíneas, ciprés, olivo, plátano de sombra y parietaria, con prestaciones similares o superiores, en el caso de alergia a polen de plátano de sombra, a las de CAP. Es especialmente útil para el diagnóstico etiológico de la polinosis en pacientes con sensibilizaciones a múltiples pólenes con periodos de polinización solapados (AU)

Clinical performance of commercial ISAC 112 allergen microarray versus noncommercial RIRAAF platform for the diagnosis of plant food and olive pollen allergies

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Is microarray analysis really useful and sufficient to diagnose nut allergy in the mediterranean area?

Background: Component-based diagnosis on multiplex platforms is widely used in food allergy but its clinical performance has not been evaluated in nut allergy. Objective: To assess the diagnostic performance of a commercial protein microarray in the determination of specific IgE (sIgE) in peanut, hazelnut, and walnut allergy. Methods: sIgE was measured in 36 peanut-allergic, 36 hazelnut-allergic, and 44 walnut-allergic patients by ISAC 112, and subsequently, sIgE against available components was determined by ImmunoCAP in patients with negative ISAC results. ImmunoCAP was also used to measure sIgE to Ara h 9, Cor a 8, and Jug r 3 in a subgroup of lipid transfer protein (LTP)-sensitized nut-allergic patients (positive skin prick test to LTP-enriched extract). sIgE levels by ImmunoCAP were compared with ISAC ranges. Results: Most peanut-, hazelnut-, and walnut-allergic patients were sensitized to the corresponding nut LTP (Ara h 9, 66.7%; Cor a 8, 80.5%; Jug r 3, 84% respectively). However, ISAC did not detect sIgE in 33.3% of peanut-allergic patients, 13.9% of hazelnut-allergic patients, or 13.6% of walnut-allergic patients. sIgE determination by ImmunoCAP detected sensitization to Ara h 9, Cor a 8, and Jug r 3 in, respectively, 61.5% of peanut-allergic patients, 60% of hazelnut-allergic patients, and 88.3% of walnut-allergic patients with negative ISAC results. In the subgroup of peach LTP-sensitized patients, Ara h 9 sIgE was detected in more cases by ImmunoCAP than by ISAC (94.4% vs 72.2%, P<.05). Similar rates of Cor a 8 and Jug r 3 sensitization were detected by both techniques. Conclusions: The diagnostic performance of ISAC was adequate for hazelnut and walnut allergy but not for peanut allergy. sIgE sensitivity against Ara h 9 in ISAC needs to be improved (AU)

Introducción: La utilidad clínica del diagnóstico por componentes no ha sido evaluada en el estudio de la alergia a frutos secos (FS). Objetivo: Evaluar la capacidad diagnóstica de una micromatriz comercial de proteínas alergénicas en la alergia a cacahuete, avellana y nuez. Métodos: Se determinó la sIgE en pacientes alérgicos a FS mediante la micromatriz ISAC 112, e ImmunoCAP en los pacientes con sIgE negativa frente a los componentes de ISAC. Además, se realizó ImmunoCAP frente a Ara h 9, Cor a 8 y Jug r 3 en un subgrupo de pacientes sensibilizados a LTP. La sIgE detectada por ImmunoCAP fue comparada con los rangos de ISAC. Resultados: La mayoría de los alérgicos a cacahuete (66,7%), avellana (80,5%) y nuez (84%) estaba sensibilizados a su LTP. Sin embargo, no se detectó sIgE frente a los componentes de ISAC en el 33,3% de alérgicos a cacahuete, 13,9% de alérgicos a avellana y 13,6% de los alérgicos a nuez. El ImmunoCAP permitió detectar sIgE a Ara h 9 en 61,5%, Cor a 8 en 60% y Jug r 3 en 83,3% de los ISAC negativo. En el subgrupo LTP, ImmunoCAP (94,4%) fue superior a ISAC (72,2%) en la detección de sIgE a Ara h 9 (p<0,05). La sIgE frente a Cor a 8 y Jug r 3 fue detectada de forma similar por ambas técnicas. Conclusiones: La micromatriz ISAC es adecuada para el diagnóstico de alergia a avellana y nuez. La sensibilidad del componente Ara h 9 de ISAC debe ser mejorada (AU)

Component-resolved diagnosis in vespid venom-allergic individuals

BACKGROUND: Hymenoptera venom-allergic patients frequently present multiple sensitisations. OBJECTIVES: To define the allergic profile by components in wasp allergic patients. To study the usefulness of specific IgE to components in cases of double sensitisation. MATERIALS AND METHODS: Wasp allergic patients who needed Polistes and/or Vespula venom immunotherapy were included. Before immunotherapy and after two years of treatment the following specific IgE (sIgE) levels were measured:Apis mellifera, Vespula spp. Polistes spp., rVes V 5, rPol d 5, nVes V 5, nPol d 5, nVes V 1, nPol d 1, nApi m 1, nApi m 2 and peroxidase. Skin tests with venoms were performed. Based on the sIgE and the skin test results, Polistes and/or Vespula immunotherapy was administered. RESULTS: Thirteen patients were included. Double sensitisation to Polistes/Vespula was detected in eight patients. Sensitisation to rVes V 5 and rPol d 5 was found in two of eight cases, to nVes V 1 and nPol d 1 in eight of 13 cases, and to nVes V 5 and nPol d 5 in 2 of 13 cases. Three patients received double immunotherapy with both wasps. One patient was treated with Vespula and nine with Polistes. sIgE levels decreased after two years of treatment. In patients who showed double sensitisation but were treated with only one venom, sIgE to both venoms decreased. CONCLUSIONS: Components analysis can be useful to study double positivity. In case of doubt, double immunotherapy should be administered. Phospholipase was found to be a major allergen in our population

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