Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens.

BACKGROUND: Low skin reactivity to common inhalant allergens is frequently found in asymptomatic individuals as well as in patients with respiratory complaints. However, most studies on bronchial allergen challenge concern patients with high levels of allergic sensitization. The present study was directed to bronchial reactions after allergen challenge in subjects with low skin reactivity to Dermatophagoides pteronyssinus or cat dander. METHODS: Titrated intracutaneous skin tests, skin prick tests, specific IgE assays, histamine release on washed leukocytes, and bronchial histamine and allergen-challenge tests were performed in 20 subjects with an intracutaneous skin test threshold for cat dander (Felis domesticus) or D. pteronyssinus above 0.1 BU/ml (mean wheal diameter in skin prick test with 10000 BU/ml: 4.4mm). Ten of the 20 patients had specific IgE below the detection limit in at least one of the three IgE assays which were done. Fifteen patients had a specific IgE level below 2 kU/I in all three tests. As a positive control group, the same parameters were studied in seven moderately sensitized patients with an intracutaneous skin test threshold below 0.1 BU/ml (mean wheal diameter with 10000 BU/ml: 7.2mm). RESULTS: The 20 subjects with low levels of allergic sensitization had an early decrease in FEV1 of 8.6% (P<0.01) and a mean late decrease of 6.3% (P<0.05). There was a trend for decrease in PC20 histamine 24h after allergen challenge (-0.4 doubling doses, P=0.09). CONCLUSIONS: In this group of subjects with low levels of allergic sensitization, a statistically significant early and late decrease in FEV1 was found. However, the decrease in lung function was small and unnoticed by most patients. The increase in nonspecific bronchial hyperresponsiveness after bronchial allergen challenge did not reach statistical significance in the study group. The results indicate that allergen exposure in patients with low levels of allergic sensitization may lead to airways changes in the absence of acute symptoms.

Differences in nonspecific bronchial responsiveness between patients with asthma and patients with rhinitis are not explained by type and degree of inhalant allergy.

Patients with allergic asthma have higher levels of nonspecific bronchial responsiveness than patients with allergic rhinitis. The aim of the study was to investigate whether this is caused by differences in the degree of allergy to inhalant allergens between asthmatics and rhinitics. Therefore, bronchial responsiveness to histamine was measured in 25 allergic patients with isolated upper airways symptoms. Nonspecific bronchial responsiveness in this group was compared with nonspecific bronchial responsiveness in a group of 136 patients with allergic asthma, with allergy and % predicted FEV1 as confounding variables. In addition, a matched pair analysis was performed. Twenty-five patients with nonallergic rhinitis served as controls to evaluate the influence of an IgE-independent inflammatory reaction in the upper respiratory tract on the level of bronchial responsiveness. Furthermore, we investigated the level of nonspecific responsiveness in 18 healthy controls. In the patients with allergic asthma, a correlation was found between nonspecific bronchial responsiveness and IgE against indoor allergens (n = 136, r = 0.34, p < 0.001) and % predicted FEV1 (n = 136, r = 0.37), p < 0.001). Patients with allergic asthma and patients with allergic rhinitis differed with respect to the level of bronchial responsiveness (p < 0.001), and the amount of specific IgE antibodies against indoor allergens (p = 0.01). The difference in level of bronchial responsiveness remained (p < 0.001) after correction with % predicted FEV1 and specific IgE against indoor allergens as confounding variables. Similarly, after matching of patients with allergic rhinitis (n = 25) with patients with allergic asthma (n = 25) regarding the specific IgE, total IgE and age of the patients, the difference in level of bronchial responsiveness remained (p < 0.001). Patients with nonallergic rhinitis had higher levels of nonspecific bronchial responsiveness than healthy controls and did not differ from patients with allergic rhinitis. In conclusion, the results confirm that IgE against common indoor allergens plays an important role in the mechanism underlying nonspecific bronchial hyperresponsiveness. However, differences in bronchial responsiveness between patients with asthma and patients with rhinitis are not merely explained by differences in the IgE antibody concentrations.

False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens.

BACKGROUND: In an outpatient population, a high frequency of positive skin prick test responses to dog dander was found in the absence of detectable IgE to dog dander in the RAST. The majority of these patients were sensitized to house dust mites (Dermatophagoides pteronyssinus) and had no obvious dog-related allergic symptoms. These findings prompted us to investigate whether dog dander skin test preparations are contaminated with house dust mite allergens in amounts sufficient to cause false-positive skin prick test responses in patients sensitized to house dust mites. METHODS: Antigen detection assays with monoclonal and polyclonal antibodies were used to determine concentrations of the major allergen Can f 1 from dog dander and the major allergens Der p 1 and Der p 2 from house dust mites in five commercially available dog dander skin prick test preparations (A to E). RESULTS: Can f 1 concentrations varied for the different extracts (A: 170 micrograms/ml, B: 11.1 micrograms/ml, C: 13.3 micrograms/ml, D: 3.8 micrograms/ml, and E: 59.4 micrograms/ml). Der p 1 was detectable in all extracts (A: 33.4 ng/ml, B:5.1 ng/ml, C:29.6 ng/ml, D: 0.4 ng/ml, and E: 1.9 ng/ml), and Der p 2 was detectable in some of the commercially available dog dander skin prick test preparations tested (A: 31.3 ng/ml, B: 3.0 ng/ml, and C: 7.5 ng/ml). The median house dust mite threshold in the skin prick test was found to be 5.8 ng/ml, of Der p 1 (range, 3.5 to 20.8 ng/ml) in nine patients tested. CONCLUSION: Contamination of commercially available dog dander skin prick test preparations with the major allergens (Der p 1 and Der p 2) of the house dust mite (D. pteronyssinus) was demonstrated. These contaminations cause false-positive responses to skin prick tests with dog dander in patients sensitized to house dust mite.

Silverfish protein in house dust in relation to mite and total arthropod level.

Two assays have been developed to measure arthropod levels in house dust. The first assay measures silverfish antigens. The second assay measures invertebrate tropomyosin and gives a global assessment of the level of arthropod-derived material. These assays and a Der p 1 and Der p 2 assay were used to analyse 53 dust samples. In most dust samples the ratio of tropomyosin/Der p 2 was higher than in mite body extract, indicating that the assay measures other arthropods besides mites. Silverfish antigen was detectable in most of the dust samples. In many homes in which the inhabitants were unaware of the presence of silverfish, silverfish antigen was detectable. Therefore for information on exposure an immunochemical analysis is superior to a questionnaire.

Fel d 1-specific IgG antibodies induced by natural exposure have blocking activity in skin tests.

Cat-allergic patients frequently have IgG antibodies directed against Fel d 1. The aim of this study was to investigate whether these IgG antibodies influence the results of the skin test. Titrated skin tests were performed with Fel d 1 and IgE and IgG antibody levels were measured in 59 patients with cat allergy. Levels of specific IgG against Fel d 1 ranged from less than 0.25 to 3.5 microgram/ml. By means of a multiple regression analysis it was shown that the amount of specific IgG antibodies contributes significantly to the results of the skin test. Presence of specific IgG against Fel d 1 was accompanied by higher skin thresholds for Fel d 1. In conclusion, this study indicates that even low levels of specific IgG, induced by natural exposure to cat allergens, have a blocking effect on the early phase skin reaction.

The relationship between RAST and skin test results in patients with asthma or rhinitis: a quantitative study with purified major allergens.

BACKGROUND: Study of the relationship between skin test results and IgE antibody levels is seriously hampered by the use of conventional allergen extracts because the precise amount of relevant allergen for each patient is unknown. OBJECTIVE: This study was designed to investigate skin reactivity with purified major allergens and to assess the relation with serum levels of IgE antibodies and to determine which additional factors contribute to the skin test result. METHODS: We used five purified major allergens (Der p 1, Der p 2, Fel d 1, Lol p 1, and Lol p 5) in skin tests, RASTs, and histamine release tests in 43 multisensitized patients with asthma or rhinitis. RESULTS: The differences in biologic activity of the five major allergens at a given level of specific IgE are within one order of magnitude. A significant residual variation remains in the correlation between skin test results and levels of IgE antibodies, which cannot be explained by imprecision of both tests (Pearson log skin test vs log specific IgE: r = 0.46-0.92). With similar levels of specific IgE, the amount of allergen that is required for a positive skin test result may differ by as much as a factor of 100 between patients. The amount of total IgE in serum contributes significantly to the skin test result. High values of total IgE are accompanied by a lower skin reactivity for allergen. Within individuals, allergens that cause skin test results that deviate from the prediction based on IgE antibody level often show a similar deviation in the histamine release test. This indicates that the type of IgE response (i.e., affinity or epitope recognition pattern) contributes significantly to the skin test result. Skin reactivity for histamine does not significantly influence the skin reactions expressed as allergen threshold. However, increased skin reactions with higher allergen dosages depend on histamine reactivity. CONCLUSION: The major allergens tested show similar biologic activities. In addition to IgE antibody level, total serum IgE and type of IgE antibody response contribute significantly to the skin test threshold for allergens. Even in a system with purified allergens, IgE antibody levels and skin test results are not interchangeable as an indicator of the degree of allergic sensitization.

IgE antibodies reactive with silverfish, cockroach and chironomid are frequently found in mite-positive allergic patients.

Approximately 30% of the house dust mite allergic patients in The Netherlands have IgE antibodies reactive with silverfish, cockroach and/or chironomid. In allergic patients without IgE antibodies against Dermatophagoides pteronyssinus less than 5% have IgE antibodies reactive with these insects. By means of RAST inhibition studies it is shown that cross-reactivity exists between D. pteronyssinus and silverfish, cockroach or chironomid. This means that a positive RAST for silverfish, cockroach, chironomid or D. pteronyssinus cannot be taken as evidence for exposure.

Food allergens in house dust.

Selected food allergens have been measured in 11 house dust samples. The amount of ovomucoid ranged from 170 to 6,300 ng/g dust. The amount of beta-lactoglobulin ranged from < 16 to 71 ng/g dust. Ovomucoid levels in some house dust samples are probably sufficiently high to cause sensitization and/or symptoms via inhalation.

Identification of a cross-reactive allergen (presumably tropomyosin) in shrimp, mite and insects.

A monoclonal antibody to Dermatophagoides pteronyssinus is described that cross-reacts with an IgE-binding antigen present in insects, Crustacea (e.g. shrimp) and other invertebrates. By means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration and immunofluorescence it was shown that this monoclonal antibody presumably recognizes tropomyosin. Tropomyosin was shown to be involved in cross-reactivity between mite, shrimp and insects in shrimp-allergic patients.

Variability of IgE-dependent histamine-releasing activity in supernatants of human mononuclear cells.

Histamine-releasing factors (HRF) that release mediators from human basophils by interacting with IgE have been identified from different cell sources, including lymphocytes, monocytes, thrombocytes and endothelial cells. These factors are studied in view of their potential importance as a stimulus in chronic inflammation. In this report we investigated the qualitative variability of the histamine-releasing activity in the supernatants of activated mononuclear cells. Purified human mononuclear cells of 8 donors were activated with streptokinase/streptodornase (SK/SD) and the supernatants (HRF-MN) were tested for histamine-releasing activity (HRA) in both allergic (RAST positive for inhalant allergens) and nonallergic individuals. Four of the eight HRF-MN supernatants were discriminating, i.e. showing no histamine-release response with nonallergic individuals, whereas four supernatants were not. Two of the HRF-MN supernatants that exhibited discriminating properties were studied in more detail. The response to HRF-MN was tested (1) in a direct bioassay on basophils of allergic (RAST positive for inhalant allergens) and nonallergic individuals and (2) in an indirect bioassay with 70% pure basophils of RAST-negative donors after passive sensitization with sera of allergic donors. An association was found between the response to HRF-MN and the RAST for inhalant allergens: none (0/12) of the RAST-negative but 15/22 of the RAST-positive individuals were HRF-MN responders. The IgE dependency of HRF-MN was shown e.g. by inhibition of passive sensitization by preincubating a responder serum with monoclonal antibody (moAb) anti-IgE MH25-1. Our results are in contrast with findings of other investigators who use pooled supernatants and demonstrated HRF-MN responsiveness with both allergic and nonallergic donors.(ABSTRACT TRUNCATED AT 250 WORDS)