Are basophil activation and sulphidoleukotriene determination useful tests for monitoring patients with peach allergy receiving sublingual immunotherapy with a Pru p 3-enriched peach extract?

INTRODUCTION: Treatment of food allergy essentially consists of food avoidance, but immunotherapy with food is emerging as a new therapeutic option. OBJECTIVE: To evaluate clinical improvement and immunological changes in patients with peach allergy following sublingual immunotherapy (SLIT) with a Prup3 quantified peach extract. METHODS: A randomized, double-blind, placebo-controlled clinical trial with peach SLIT was conducted. We assessed clinical efficacy after 6 months of treatment by means of double-blind, placebo-controlled oral challenges with peach and also evaluated immunological changes (basophil activation test [BAT] and determination of sulphidoleukotriene production) following stimulation with peach peel and pulp, rPrup3, rMald 1, and rMal d 4 stimulation. We also measured specific IgE and IgG4 to Pru p3. RESULTS: After 6 months of SLIT (T6), the active group showed a 3-fold improvement in tolerance to Prup3 and a significant increase in IgE to rPrup3 and in sLT production following stimulation with peach peel and rPrup3. There was also a significant increase in BAT results after stimulation with rPrup3 at 1 month of SLIT (T1). Statistically significant between-group differences were only observed for BAT with peach peel and pulp at T1 and T6 and for BAT with rPru p3 at T6. No changes were observed in BAT with rMal d 1 or rMal d 4 or in IgG4 levels to nPrup3. CONCLUSIONS: SLIT with a Pru p 3 quantified peach extract is clinically effective and leads to an increase in basophil activation and sulphidoleukotriene production following stimulation with rPru p3 and peach peel in the first months of treatment.

Cross-reactivity syndromes in food allergy.

The immunological phenomenon of cross-reactivity has consequences for the diagnosis and treatment of certain food allergies. Once allergy to a particular food has been confirmed, positive test results are often obtained against other foods and, although less frequently, true clinical cross-reactivity is determined. This article reviews the relevant clinical aspects of food allergies in which the underlying mechanism is cross-reactivity between foods that are both related and unrelated taxonomically.

Oleaceae-induced pollinosis in an area with exposure to olive and ash trees.

BACKGROUND: Navarre, in Northern Spain, is an area with moderate exposure to olive and ash tree pollen. OBJECTIVE: To assess the relevance of ash as a cause of pollinosis in our region. METHODS: The study sample comprised 85 patients from Navarre with clinical symptoms of pollinosis. Specific immunoglobulin E (sIgE) was determined to Fra e 1, Ole e 1, and a mixture of amino- and carboxy-terminal domains of Ole e 9 (Ole e 9 NC) (ADVIA-Centaur). At the same time, the presence of sIgE to other pollen allergens was studied. Prick tests were performed with ash pollen (n=33) and olive pollen (n=85) and the symptomatic period was recorded (n=85). As a control group, we studied the serum of 98 patients with olive pollen allergy, intense exposure to olive pollen, and no exposure to ash. RESULTS: Sensitization to Oleaceae was detected in 24/85 patients in the study group (28.2%). In this group, the mean (SD) level of IgE to Fra e 1 was 8.5 (10) kU(A)/L and to Ole e 16.07 (7.88) kU(A)/L (P < .001). In the control group, these figures were 103.64 (132.19) kU(A)/L and 86.43 (118.5) kU(A)/L (P < .001), respectively. In all patients with positive sIgE to Fra e 1, IgE to Ole e 1 was also detected (concordance index, kappa = 1), both in the study group and in the control group. Patients who were sensitized to Fra e 1 did not present a longer symptomatic period and their symptoms did not have an earlier onset. CONCLUSION: We did not find evidence of clinically relevant sensitization to ash in Navarre.

Biological standardization and maximum tolerated dose estimation of an Alternaria alternata allergenic extract.

BACKGROUND: The manufacture of allergenic extracts from the mold Alternaria alternata is influenced by factors such as strain variability, allergenic origin, culturing conditions and extraction process, which affect the reproducibility of the preparations intended for diagnostic and therapeutic use. OBJECTIVES: To select the most adequate antigenic source of A. alternata extracts and determine its maximum tolerated dose (MTD) to be used in a subsequent immunotherapy efficacy clinical trial. METHODS: Twenty-one patients monosensitized to A. alternata were involved in a biological standardization process of A. alternata extracts. Four different mold strains were cultured and used to produce extracts by three different methods, each incorporating proteins from different origins: culture filtrate, buffer extractable fraction and cellular antigens. The selected extract, characterized as in-house reference (IHR) preparation was used in a MTD finding immunotherapy study. Serum IgE, IgG, IgG1 and IgG4 specific of complete extract and purified natural and recombinant forms of Alt a 1 were determined by different EIA methods. RESULTS: Culture filtrate extract containing the allergens secreted to the spent medium was shown to be the most adequate option for establishing an IHR preparation for A. alternata extract manufacturing. A maximum dose of 1670 UBE, equivalent to 0.1 microg Alt a 1, was determined as MTD for immunotherapy. One year of administration of such a dose at monthly intervals elicited pronounced immunological changes with statistically significant decreases in IgE and increases in IgG4, both estimated with whole extract or purified Alt a 1. CONCLUSION: A high quality natural A. alternata extract has been developed and preliminarily tested to define its MTD for subsequent determination of the optimal dose in an immunotherapy efficacy clinical trial.

[Treatment of allergy to mushrooms]. / Tratamiento de la alergia a hongos.

The treatment of patients with respiratory allergy is based on environmental control measures, pharmacological and immunotherapy treatment. The third cause of allergic respiratory disease in our environment is mushrooms, the most frequently involved being the Alternaria class. However, due to the great difficulties in their diagnosis and specific treatment, there are few controlled studies on immunotherapy with mushroom extracts. A clinical test was carried out with a suitable, biologically standardized extract for the diagnosis and treatment of patients allergic to Alternaria. A second phase determined the maximum tolerated dosage of this extract administered through immunotherapy, in depot preparation and in conventional dosage, which was 0.1 mg/ml of Alt a I. This dosage was established as the maintenance dosage in the following phase (double blind test controlled with placebo), in which the efficacy and safety of the immunotherapy with this extract was determined, administered in immunotherapy to the mentioned maintenance dosage, to 28 patients with rhinitis and/or asthma due to allergy to Alternaria. All the patients reached the pre-established maintenance dosage of 1670 BSU. The treatment proved efficient, producing an improvement in the symptoms, respiratory function, subjective evaluation of patient and doctor, and severity of the disease. The immunological response supported the clinical efficacy, with an increase in the IgG and a fall in the IgE over the course of the study. Tolerance to the treatment was excellent, with only two light systemic reactions registered in the 711 dosages administered (0.28% reactions/dosages administered).

Identification of allergens involved in occupational asthma due to carmine dye.

BACKGROUND: Carmine has been implicated as an etiologic agent of occupational asthma, but the allergens involved have not been yet identified. OBJECTIVE: To identify the allergens involved in occupational asthma due to carmine dye. METHODS: An in vitro study based in SDS-PAGE and IgE immunoblotting with carmine and cochineal extracts was performed. Sera from three carmine dye workers diagnosed with occupational asthma induced by carmine dye and from seven nonatopic subjects were used. RESULTS: Three proteins of around 30, 28, and 17 kD in raw cochineal extract and another protein of 50 kD in the boiled one were demonstrated by SDS-PAGE. Two proteins of around 50 and 28 kD were observed in the carmine extract by the same technique. Specific IgE binding bands at 17 kD in cochineal raw extract, at 50 kD in the boiled one, and at 28 kD in carmine extract were demonstrated by IgE immunoblotting. CONCLUSIONS: We have identified three allergens of around 17, 28, and 50 kD implicated in occupational asthma of three carmine workers.

Tolerance of immunotherapy with a standardized extract of Alternaria tenuis in patients with rhinitis and bronchial asthma.

We studied the safety of immunotherapy with an Alternaria extract in patients with rhinitis and bronchial asthma. The few studies that have investigated immunotherapy with mold allergens suggest that they cause adverse reactions more frequently than do other extracts. All treatments prescribed by our allergology service with Alternaria immunotherapy between 1988 and 1996 were recorded and analyzed. In all cases a biologically standardized depot extract of Alternaria tenuis containing 5 BU/ml was used according to a conventional immunotherapy schedule. During the study period 129 patients received immunotherapy with Alternaria extract. Of the 3,892 doses given, 1.95% led to adverse reactions, which occurred in 39.5% of the patients. Most of the adverse reactions were systemic and mild, and reproduced the underlying disease. The risk of adverse reactions was significantly higher in children, patients with asthma, and during the initial phase of treatment. Patients who suffered from adverse reactions had a significantly higher level of total and specific IgE. It was concluded that tolerance of Alternaria mold extract was worse than for other allergenic extracts, although most reactions recorded were mild. The risk of adverse reactions was greater in children and patients with asthma, and during the initial phase of immunotherapy.

Cluster versus conventional immunotherapy in patients allergic to Dermatophagoides pteronyssinus: a controlled study of in vivo and in vitro parameters.

We designed a cluster schedule of immunotherapy for patients allergic to Dermatophagoides pteronyssinus which showed good safety and clinical efficacy. Here we compare the in vivo and in vitro changes with those of a conventional schedule in a controlled trial. Sixty-three patients were randomized as follows: 29 were treated with the cluster schedule, 15 with a conventional schedule and 19 received no immunotherapy. A standardized extract was used. Changes in in vivo parameters (skin prick test and conjunctival provocation test) and in in vitro parameters (IgE, IgG, IgG1 and IgG4 for the complete extract, Der p 1 and Der p 2) were measured before immunotherapy (T0), on reaching maintenance phase (T1), and after 6 (T2), 12 (T3) and 18 months of maintenance (T4). Cutaneous reactivity showed a significant decrease from T1 in both the cluster and conventional schedules, and conjunctival reactivity was also significantly lowered from T1 in these groups. Specific IgE decreased and specific IgG, IgG1 and IgG4 increased significantly from T1 in the cluster and conventional schedules. Neither of these parameters showed any changes in the group without immunotherapy. In conclusion, our cluster schedule induced changes in cutaneous and conjunctival reactivity and in immunological parameters that were similar to those achieved with the conventional schedule; these changes did not appear in patients who did not undergo immunotherapy.

Diversity of allergens causing occupational asthma among cereal workers as demonstrated by exposure procedures.

BACKGROUND: Occupational asthma among cereal workers is frequently due to cereals but other allergens can also be responsible. OBJECTIVE: We evaluated the allergens causing occupational asthma in the patients who had been diagnosed in our Department during the last 5 years. Specific bronchial reactivity to the implicated allergens was assessed and compared by standardized bronchial challenge. METHODS: Twenty-one patients (12 bakers, three millers and six farmers) were studied. We carried out in vivo tests (skin and challenge tests) and in vitro tests (specific IgE measurement) with cereals, enzymes, soyabean, storage mites and egg. A definitive diagnosis was established by means of specific bronchial provocation tests (BPT), except in three patients in whom it could not be carried out due to the severity of their asthma. In these cases the causative agent had to be determined by means of conjunctival challenge. RESULTS: Cereals were the main sensitizers among bakers (75%) and farmers (66%). Bakers were also sensitive to alpha-amylase (41%) and soyabean (25%), and farmers, to soyabean (33%) and storage mites (33%). Occupational asthma was due to cereals, soyabean and storage mites among millers. CONCLUSIONS: Besides cereals, other allergens such as enzymes, leguminous, egg and storage mites can be the causative agents of occupational asthma among cereal workers. Sensitization to different allergens in the different jobs is very likely due to differences in exposure.