The Lights and the Shadows of Controlled Sting Challenge With Hymenoptera.

Hymenoptera venom immunotherapy (VIT) is effective for protecting individuals with systemic allergic reactions caused by Hymenoptera stings. The need for a tool that shows the degree of protection afforded by VIT and the lack of useful biomarkers have made the sting challenge test (SCT) the gold standard for this disorder, although its use has both lights and shadows. SCT with Hymenoptera involves causing a real sting in a patient diagnosed with allergy to the venom of the stinging insect and who is undergoing treatment with specific immunotherapy. In Spain, SCT is included in the list of services offered by some hospitals and forms part of their daily clinical practice. This review aims to analyze the strengths and weaknesses of this test and to describe the standardized procedure and necessary resources, based on the experience of a group of Spanish experts and a review of the literature.

Helios-Negative Regulatory T Cells as a Key Factor of Immune Tolerance in Nonallergic Beekeepers.

BACKGROUND AND OBJECTIVES: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. METHODS: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. RESULTS: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P<.001), together with a high basophil activation rate (P<.001). Conversely, compared with APs, TBKs had higher levels of sIgG4 (P<.001) and IL-10 (P<.0001), as well as an enhanced CTLA-4+ Treg population (P=.001), expanded Helios- Treg (P<.003), and reduced type 1 helper T cells (TH1) (P=.008), TH2 (P=.004), and TH17 (P=.007) subsets. CONCLUSIONS: The profile of TBKs, which was strongly marked by Treg activity, differed from that of TBKs. This natural tolerance would be led by the expansion of inducible Helios- Treg cells at the peripheral level. The Helios- Treg population could be a novel candidate biomarker for monitoring tolerance.

The Lights and the Shadows of Controlled Sting Challenge With Hymenoptera

Hymenoptera venom immunotherapy (VIT) is effective for protecting individuals with systemic allergic reactions caused by Hymenopterastings. The need for a tool that shows the degree of protection afforded by VIT and the lack of useful biomarkers have made the stingchallenge test (SCT) the gold standard for this disorder, although its use has both lights and shadows. SCT with Hymenoptera involvescausing a real sting in a patient diagnosed with allergy to the venom of the stinging insect and who is undergoing treatment with specificimmunotherapy. In Spain, SCT is included in the list of services offered by some hospitals and forms part of their daily clinical practice. Thisreview aims to analyze the strengths and weaknesses of this test and to describe the standardized procedure and necessary resources,based on the experience of a group of Spanish experts and a review of the literature. (AU)

La inmunoterapia con veneno de himenóptero (ITV) es un tratamiento que se ha mostrado eficaz en la protección de sujetos con reaccionesalérgicas sistémicas por picaduras de himenópteros. La necesidad de una herramienta que demuestre el grado de protección proporcionadapor la ITV, y la ausencia de biomarcadores útiles, convierte a la Prueba de Provocación con Repicadura (PPR) en el gold standard en estapatología, con sus luces y sus sombras. La PPR con himenópteros es una prueba que consiste en provocar una picadura real, a un pacienteque ha sido diagnosticado de alergia al veneno del insecto picador y habitualmente está en tratamiento con inmunoterapia específica.En España, la PPR se incluye en la cartera de servicios de algunos hospitales, formando parte de su práctica clínica habitual. Esta revisióntrata de analizar las fortalezas y debilidades de esta prueba, integrando el procedimiento estandarizado y recursos necesarios, basándoseen la experiencia de un grupo de expertos españoles y en la revisión de la literatura. (AU)

Helios-Negative Regulatory T Cells as a Key Factor of Immune Tolerance in Nonallergic Beekeepers

Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P<.001), together with a high basophil activation rate (P<.001). Conversely, compared with APs, TBKs had higher levels of sIgG4 (P<.001) and IL-10 (P<.0001), as well as an enhanced CTLA-4+ Treg population (P=.001), expanded Helios– Treg (P<.003), and reduced type 1 helper T cells (TH1) (P=.008), TH2 (P=.004), and TH17 (P=.007) subsets. Conclusions: The profile of TBKs, which was strongly marked by Treg activity, differed from that of TBKs. This natural tolerance would be led by the expansion of inducible Helios– Treg cells at the peripheral level. The Helios– Treg population could be a novel candidate biomarker for monitoring tolerance (AU)

Successful adaptation of bee venom ommunotherapy in a patient monosensitized to api m 10

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Quality Standards for Allergen Immunotherapy Clinics in Spain: Consensus Document.

BACKGROUND AND OBJECTIVE: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. Objective: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology.

Quality standards for allergen immunotherapy clinics in Spain: consensus document

BACKGROUND: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. OBJECTIVE: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology

ANTECEDENTES: Las unidades de inmunoterapia (UIT) en España son muy diferentes en cuanto a estructura, organización, recursos y cartera de servicios. Por ello, resulta esencial homogeneizar criterios de actuación y definir estándares de calidad para las UIT de mayor complejidad. OBJETIVO: Establecer recomendaciones que permitan garantizar la calidad y seguridad en la administración de la inmunoterapia y definir estándares de calidad para las UIT de mayor complejidad. MÉTODOS: Proyecto iniciado (año 2013) con una encuesta on-line a 65 servicios o unidades de alergología de toda España. Posteriormente, se desarrolló un proceso de consenso en dos fases. En la primera, diez expertos definieron y consensuaron los estándares mediante el método RAND/UCLA; en la segunda, los acuerdos se validaron mediante una consulta Delphi a dos rondas con 84 expertos. RESULTADOS: Se consensuaron criterios mínimos de seguridad y calidad en la administración de inmunoterapia con alérgenos (ITA) y se definieron dos niveles de UIT de mayor complejidad: las UIT acreditadas (UITA) y las UIT acreditadas con excelencia (UITAE), consensuándose también los estándares de calidad y criterios de acreditación para ambos niveles. CONCLUSIONES: Proyecto pionero en su objetivo - definición de estándares de calidad de UIT- y en el empleo de técnicas de participación estructuradas -combinación de los métodos RAND/UCLA y Delphi-. El resultado es la definición de unos mínimos de calidad y seguridad para administrar ITA, y un conjunto de criterios de calidad para la acreditación de las UIT que cuenta con el respaldo de un amplio panel de expertos de la SEAIC

Component-resolved diagnosis in hymenoptera allergy

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy

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Component-resolved diagnosis in hymenoptera allergy.

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.

Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics.

BACKGROUND: Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups. METHODS: The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test (BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas. RESULTS: All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization. CONCLUSIONS: Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy.

Diagnosis of patients with immediate hypersensitivity to beta-lactams using retest.

BACKGROUND: beta-Lactams are the drugs most frequently involved in hypersensitivity reactions mediated by immunoglobulin (Ig) E. OBJECTIVE: To evaluate a population of patients with suspected B-lactam allergy using a validated algorithm that includes specific IgE antibodies, skin testing, and/or a drug provocation test. METHODS: A total of 1032 patients with symptoms compatible with B-lactam allergy were evaluated by means of their clinical history, specific immunoglobulin (Ig) E antibody determinations (benzylpenicillin, ampicillin, and amoxicillin), and skin tests with major determinants (penicilloyl-polylysine) and minor determinants (minor determinant mixture) of benzylpenicillin, penicillin G, ampicillin, and amoxicillin-clavulanic acid. Patients whose skin test results were negative were challenged with amoxicillin-clavulanic acid. Only immediate hypersensitivity reactions were evaluated. All patients with negative study results and for whom a reaction occurred more than 1 year before were retested using the same protocol. RESULTS: A total of 170 patients (16.4%) were finally confirmed as having immediate allergic reactions to beta-lactams (62.3% by skin testing, 16.5% by specific IgE, and 21.2% by drug provocation test). The mean age of these patients was 43.3 years, and the drug most frequently involved in the reaction was amoxicillin (41.1%), followed by the combination amoxicillin-clavulanic acid (36.4%). In the remaining 22.5%, different beta-lactams were involved or the culprit drug was not known. Only mild reactions were observed after the drug provocation test. A retest was required in 23% of patients in order to confirm their hypersensitivity. CONCLUSIONS: These results indicate that a diagnostic protocol based on the combination of skin testing and in vitro determination of specific IgE antibodies plus, if required, drug provocation testing is an appropriate procedure for evaluating immediate hypersensitivity reactions to beta-lactams. Because the sensitivity of skin testing and in vitro IgE assays is not optimal and a considerable proportion of patients are tolerant, drug provocation tests are necessary to achieve the diagnosis or confirm tolerance. A large percentage of patients (23%) were diagnosed using retest.

Safety of two cluster schedules for subcutaneous immunotherapy in allergic rhinitis or asthma patients sensitized to inhalant allergens.

BACKGROUND: Subcutaneous immunotherapy (SCIT) usually requires a long titration phase, which can be associated with various adverse events (AEs). OBJECTIVES: It was the aim of this study to determine the safety of 2 cluster regimens for SCIT in patients with allergic rhinitis, with or without mild or moderate allergic asthma, who were sensitized to grass and/or tree pollen, or house dust mites (HDM). PATIENTS AND METHODS: Adult patients were included in a European, open-label, prospective trial. Pollen-allergic patients received grass pollen, grass and olive pollen, or hazel, alder and birch pollen according to a 3-week titration cluster. HDM-allergic patients received HDM extract according to a 2-week titration cluster. The safety of the titration phase was assessed in terms of local and systemic AEs. RESULTS: The safety analysis included 157 patients: 110 received pollen and 47 HDM extract. During the cluster titration, 248 AE episodes were reported in the pollen group and 113 in the HDM group; these were mainly local reactions. Around one third of patients (30.9% pollen and 38.3% HDM) did not experience any AE. In most cases (67.1% of pollen and 71.1% of HDM patients), AEs did not lead to a change in titration schedule. No anaphylactic reaction or other serious life-threatening systemic AEs were reported. Only 2 patients in the HDM group discontinued treatment because of AEs. CONCLUSIONS: Rapid cluster titration was well tolerated in adults with allergic rhinitis, with or without mild to moderate allergic asthma, due to pollen or HDM. This short-titration, high-dose cluster regime may allow better patient compliance and cost savings.

Improving pollen immunotherapy: minor allergens and panallergens.

Multiple sensitizations to pollens are common clinical situations in Spain, and alter the efficacy of allergen-specific immunotherapy. We now know that optimization of the diagnosis is required to define the best suited treatment for each patient. All pollen allergens belong to 29 families of proteins - the most abundant being the expansins, prophyllins and polcalcins. The ubiquitous nature of proteins such as the prophyllins and polcalcins defines them as panallergens, and explains the cross-reactivity that is erroneously interpreted by clinicians as constituting multi-sensitization. Other families of allergens, such as the calcium transporting proteins (LTPs) are more restricted, but are associated to severe types of allergic disease - this being particularly useful to decide upon the indication of immunotherapy. Although recombinant allergens can be produced for in vitro diagnostic purposes, current legislation only allows the use of natural proteins for immunotherapy. However, the same technology can be applied to the study of extracts for vaccines, and it seems that allergen quantification by the manufacturers is a no return trip which clinicians are obliged to follow.

Improving pollen immunotherapy: minor allergens and panallergens

Multiple sensitizations to pollens are common clinical situations in Spain, and alter the efficacy of allergen-specific immunotherapy. We now know that optimization of the diagnosis is required to define the best suited treatment for each patient. All pollen allergens belong to 29 families of proteins ­ the most abundant being the expansins, prophyllins and polcalcins. The ubiquitous nature of proteins such as the prophyllins and polcalcins defines them as panallergens, and explains the cross-reactivity that is erroneously interpreted by clinicians as constituting multi-sensitization. Other families of allergens, such as the calcium transporting proteins (LTPs) are more restricted, but are associated to severe types of allergic disease ­ this being particularly useful to decide upon the indication of immunotherapy. Although recombinant allergens can be produced for in vitro diagnostic purposes, current legislation only allows the use of natural proteins for immunotherapy. However, the same technology can be applied to the study of extracts for vaccines, and it seems that allergen quantification by the manufacturers is a no return trip which clinicians are obliged to follow

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Mejorando la inmunoterapia con pólenes: alergenos minoritarios y panalergenos / No disponible

La sensibilización múltiple a pólenes es una situación clínica frecuente en España que condiciona la eficacia de la inmunoterapia alérgeno-específica. Hoy sabemos que se necesita optimizar el diagnóstico para seleccionar el tratamiento adecuado para cada paciente. Abordar la alergología a nivel molecular aparentemente complica el manejo asistencial y sin embargo, basta cruzar los registros de una base de datos de familias de proteínas secuenciadas1 con los de otra de alergenos conocidos , para obtener un número limitado de proteínas alergénicas que a su vez pueden ser clasificadas por su origen taxonómico3. La información final puede consultarse de forma integrada en otra base de datos4 que actualiza ágilmente lo referente a características bioquímicas, origen, función biológica, documentación clínica y disponibilidad industrial de alergenos. Todos los alergenos polínicos pertenecen a 29 familias de proteínas, siendo las más abundantes las expansinas, profilinas y polcalcinas. La naturaleza ubicua de proteínas como las profilinas y polcalcinas les confieren carácter de panalergenos y explica la reactividad cruzada, que es interpretada erróneamente por los clínicos como multisensibilidad. Otras familias de alergenos, como las proteínas transportadoras de calcio (LTPs), son más restringidas pero se asocian a un perfil de especial gravedad clínica, lo que resulta especialmente útil a la hora de indicar la inmunoterapia. El diagnóstico más preciso lo dan las proteínas muy selectivas de especie, como las expansinas de las gramíneas. Aunque es posible la fabricación de alergenos recombinantes para el diagnóstico in vitro, la legislación actual sólo permite el uso de proteínas naturales para inmunoterapia. Sin embargo, es posible aplicar la misma tecnología al estudio de los extractos para vacunas, y parece que la cuantificación de alergenos por parte de los fabricantes es un camino sin retroceso que los clínicos estamos obligados a seguir (AU)

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[Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters]. / Inmunoterapia con un extracto oral de Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusiones sobre parámetros in vivo e in vitro.

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.

Inmunoterapia con un extracto oral del Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusines sobre parámetros in vivo e in vitro / Immunotherapy with an oral Alternaria extract in chilhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro

Ante la escasez de trabajos con inmunoterapia oral de Alternaria, planteamos la realización de un ensayo clínico en 39 pacientes, con edades comprendidas entre 7 y 17 años, alérgicos a Alternaria, y sensibilizados también a pólenes y epitelios para evaluar su eficacia clínica y seguridad, así como las repercusiones sobre parámetros in vivo e in vitro. Se empleó un extracto estandarizado, determinando la actividad alérgica mediante RAST inhibición y prick test cutáneo. La cuantificación del alergeno principal (Alt a 1) se llevó a cabo mediante la técnica de fijación en dos lugares, siendo el contenido medio de 34,2 ng Alt a 1/ g de proteína. Los parámetros analizados fueron la puntuación de síntomas-medicación, prick test cutáneo a punto final (TC), test de bronco provocación específico (TBPE), pico de flujo (PF), IgE total y específica e IgG4.Diecinueve pacientes recibieron tratamiento activo con inmunoterapia oral (ITO) y otros diecinueve recibieron tratamiento sintomático. La fase de inicio de la inmunoterapia duró 3 meses, hasta llegar a dosis máxima, que se mantuvo durante 12 meses, alcanzando una dosis acumulada media de 280.000 PNU. Se hallaron diferencias significativas en la disminución de la puntuación de síntomas-medicación en el grupo tratado, tras los 12 meses de inmunoterapia (ITO). No se encontraron diferencias en el grupo control. La inmunoterapia fue bien tolerada, presentando 0,42 reacciones adversas (RA) por 100 dosis administradas, siendo de carácter leve-moderado exclusivamente. Se encontró disminución significativa del tamaño de pápula en el grupo tratado. El TBPE expresado mediante la PD20 mostró cifras significativamente más altas en el grupo con ITO. El pico de flujo no mostró cambios en ninguno de los dos grupos. Los valores de la IgG4 fueron significativamente más altos en el grupo con inmunoterapia. Los niveles de IgE total y específica no mostraron cambios significativos en ambos grupos. En conclusión, la Inmunoterapia Oral con extracto de Alternaria ha demostrado eficacia clínica en pacientes pediátricos, siendo en general bien tolerada, modificando la reactividad específica cutánea y bronquial con incremento de los niveles de IgG4 específica implicados en la respuesta humoral (AU)

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/μg protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response (AU)