Evaluation of the nasal provocation test for its necessity in the diagnosis of nasal allergy to house dust mite

The aim of this study was to evaluate rhinomanometric responses to nasal allergen provocation in children with allergic rhinitis sensitized to house dust mite. We studied 51 children, aged 6-16 years (mean: 11.5 +/- 2.6 years), with clinical symptoms of perennial allergic rhinitis without asthma and 20 non-atopic healthy controls in the same age range (mean: 11.8 +/- 3.8 years). All of the patients had positive skin prick test (SPT) results and serum specific IgE above 0.70 kU/l to Dermatophagoides pteronyssinus (Dp). Nasal provocation testing (NPT) was performed with increasing concentrations of Dp extracts and the nasal response was evaluated by active anterior rhinomanometry. A 100% increase of resistance in one or both nasal cavities was considered positive. There was a statistically significant difference of baseline nasal resistance (total, right and left sides) between the control and the patient groups (p < 0.001). A positive response to house dust mite allergens was recorded in 47/51 (92.2%) patients by rhinomanometry. The NPT presented no significant correlation with age, weight, height, SPT diameter, serum total and specific IgE levels to Dp and baseline nasal airway resistance values. This study suggests that a nasal provocation test with allergen is unnecessary in children with positive skin prick test and serum IgE specific to house dust mite. The rhinomanometric response to the allergen provocation does not correlate with the diameter of the skin prick test and the level of serum specific IgE.     

Sensitization to Blomia tropicalis and dermatophagoides pteronyssinus-a comparative study between Singapore and Taiwan

Blomia tropicalis (Bt) and Dermatophagoides pteronyssinus (Dp) are the predominant domestic mites species in Singapore and Taiwan. This study aims to characterize and compare the mite sensitization profiles in both countries. Skin prick tests were performed on 203 Singaporeans with Dp and Bt crude extracts. In vitro IgE and IgG4 reactivity to extracts and specific allergens (Der p 1, Der p 2 Der p 5 and Blo t 5) were determined by immunoassays. Approximately 91% of the tested Singaporeans were skin test positive for both Bt and Dp. Both populations share similar frequencies of in vitro IgE reactivity to all the allergens tested, but they differ in the pattern and magnitude of allergen sensitization. Although Der p 1, Der p 2 and Blo t5 are major sensitizing allergens in both countries, Blo t 5 is a more potent one in Singapore, probably reflecting the high level of exposure to Bt. The unique major Bt and Dp allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in both countries.     

Prevalence of specific IgE to the storage mite, Aleuroglyphus ovatus

Aleuroglyphus ovatus (Ao) is a storage mite that has a worldwide distribution and has been found in stored bran, wheat, chicken meal, and dried fish products. Ao was isolated from a chicken meal sample, cultured on whole wheat flour at 75% relative humidity, and 1 gm of pure Ao bodies were extracted, 1:20 wt/vol, in 0.2 mol/L of ammonium bicarbonate. Der p I, major allergen of Dermatophagoides, pteronyssinus (Dp), or Der f I major allergen to Dermatophagoides farinae (Df), was not detected in extracts of Ao. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed 25 bands (6 to 110 kd), and thin-layer isoelectric focusing revealed 19 bands (isoelectric point, 3.5 to 9.3). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots with six different sera identified nine IgE binding bands (16 to 100 kd). Thin-layer isoelectric focusing immunoblots identified 16 IgE binding bands (isoelectric point, 4.5 to 9.3). An aliquot of the Ao extract was diluted in bicarbonate buffer (pH 9.2) and adsorbed to plastic microtiter plates. RAST to Ao and Dp were performed with sera of 163 atopic individuals (88 with allergic rhinitis and 75 with allergic asthma with or without allergic rhinitis). All individuals had appropriately positive skin tests that correlated with a history of exacerbation secondary to allergen exposure. RAST results to Dp and Ao were analyzed by regression analysis (r = 0.64; p = 0.0001). Fifty-five individuals were RAST positive to Dp alone, 32 to Ao and Dp, and three to Ao alone; 73 individuals were negative to Ao and Dp. RAST inhibition demonstrated moderate cross-reactivity between Ao and Dp.     

Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach?

BACKGROUND: The pathogenic importance of the ubiquitous house dust mite, Dermatophagoides pteronyssinus (Dp), in atopic dermatitis is unclear. OBJECTIVE: We aimed to explore the relevance of Dp hypersensitivity in adult patients with atopic dermatitis by using an in vivo topical challenge method and in vitro assays for T-cell reactivity. METHODS: Dp and control skin prick test solutions were applied to the cubital fossae of 20 patients twice daily for 4 days; the severity of dermatitis and pruritus in the challenge sites were determined before and after testing. The same solutions were used in PBMC proliferation assays that included 10% fresh, autologous serum, the latter aimed at maximizing IgE facilitated allergen presentation. RESULTS: Although most patients had markedly elevated Dp-specific serum IgE levels, only 6 of 20 patients developed increases in cubital fossa dermatitis severity and pruritus scores that were greater at sites of application of Dp solution than at control sites. In addition, PBMC proliferation in response to Dp solution in the presence of autologous serum was significantly greater in the in vivo challenge-positive patients than in those who did not respond to challenge. A subgroup of patients (7/20) also developed transient but pronounced contact urticaria at sites of Dp application. CONCLUSION: These findings suggest that hypersensitivity to Dp might be clinically relevant in approximately one third of the adult atopic dermatitis population studied. They also point to methods of identifying patients who might respond to house dust avoidance measures.     

Protein sequence analysis of a novel 103-kDa Dermatophagoides pteronyssinus mite allergen and prevalence of serum immunoglobulin E reactivity to rDer p 11 in allergic adult patients

BACKGROUND: House dust mites are regarded as important indoor allergens. While the most studies mite allergens are low molecular weight (mw), a high mw Dermatophagoides farinae mite paramyosin (Der f 11) has recently been cloned. We have also cloned a novel high mw Dermatophagoides pteronyssinus (Dp) mite allergen, Der p 11. OBJECTIVE: The aim of this study was to isolate and express a cDNA gene coding for a Der p 11 allergen, to compare the sequence of Der p 11 with other antigens and to evaluate the presence of IgE reactivity to the recombinant protein (rDer p 11) in the sera of allergic adult patients. METHODS: The full-length Der p 11 gene was isolated by cDNA library screening, 5'-3' rapid amplification of cDNA ends and PCR. The cDNA gene was expressed as a glutathione-S-transferase fusion protein in Escherichia coli. The allergenicity of rDer p 11 was tested by human IgE immunodot or immunoblot assay in a large panel of 100 allergic patients with bronchial asthma, allergic rhinitis or eczema. RESULTS: Der p 11 is a 2965 bp cDNA gene with a 2625 bp open reading frame coding for a 875 amino acid protein. The deduced amino acid sequence of the Der p 11 showed significant homology with various invertebrate paramyosins. The prevalence of serum IgE reactivity to rDer p 11 on immunodot assay ranged from 41.7% to 66.7% in different allergic patient groups, whereas it was rare in non-atopic patients with urticaria (18.8%) and in normal individuals (8%). A high frequency (five out of eight) of MAST(Dp)- allergic serum samples had specific IgE-binding activity to rDer p 11 or its fragments on immunoblot assay, even though their IgE-binding activity to Dp extract was either weak or negative. CONCLUSION: The 103-kDa Der p 11 appears to be major Dp mite allergen with a high frequency of IgE reactivity in sera of patients allergic to mites.     

Recent advances in the diagnosis of allergic rhinitis

ABSTRACT

Introduction: Allergic rhinitis (AR) is a disorder with high prevalence worldwide. Identification of clinically relevant allergens is the key step for the diagnosis, allergen avoidance and allergen specific immunotherapy for AR.

Areas covered: With the new findings of mechanisms of AR and the development of technology, much progress has been achieved in the diagnosis of AR recently. We review the recent advances about local IgE, in vivo and in vitro tests, cytological diagnosis and nitric oxide (NO) in the diagnosis of AR.

Expert commentary: AR is traditionally diagnosed with the combined evaluation of history and allergen sensitization by in vivo skin prick tests and in vitro allergen specific IgE in serum, to confirm the correlation between clinical history and potential allergens. Nasal provocation test and local IgE measurement can be used to diagnose local AR. Allergen microarray has the ability to detect more potential allergens. Basophil activation and mast cell activation tests can be used in allergen diagnosis and to modify the response to immunotherapy, while cytological diagnosis is useful in the differential diagnosis of AR and non-AR. Nasal NO has been confirmed to be an optimal biomarker to discriminate between AR and non-AR.     

Citrus red mite (Panonychus citri) is the most common sensitizing allergen of asthma and rhinitis in citrus farmers.

OBJECTIVE: To evaluate type I hypersensitivity to citrus red mite (Panonychus citri), its prevalence, and relationship to respiratory dysfunction, a cross-sectional survey was performed among citrus farmers on Cheju Island, Korea. MATERIALS AND METHODS: Questionnaires, and skin prick test responses to 11 common inhalant allergens and citrus red mite were performed in 181 citrus farmers, and serum-specific IgE antibodies to citrus red mite were measured by ELISA in sera of 123 subjects. To determine airway hyperresponsiveness, methacholine bronchial provocation tests were performed in 55 subjects who complained of recurrent lower respiratory symptoms. RESULTS: The prevalence of asthma-based on presence of asthmatic symptoms on the questionnaire and airway hyperresponsiveness to methacholine, and allergic rhinitis based on presence of nasal symptoms on the questionnaire and positive skin-test response were 12.1% and 19.3%, respectively. The positive rate of skin responses to one or more of 11 common inhalant allergens excluding citrus red mite was 17.1%, and if citrus red mite was included, 25.9% of farmers had positive responses. On skin prick tests, citrus red mite (16.5%) was the most common sensitizing allergen, followed by cockroach (11.0%), Dermatophagoides pteronyssinus (9.9%), and D. farinae (9.3%). Among farmers with asthma and allergic rhinitis, the positive skin responses to citrus red mite were noted in 54.5 and 68.5%, respectively. Serum-specific IgE antibodies to citrus red mite were detected in 45 farmers (36. 5%) of the 123 tested, and there was significant correlation between specific IgE level and weal (A/H ratio) to citrus red mite (r = 0.57, P < 0.001). The prevalence of asthma was higher in subjects with positive skin responses or high serum-specific IgE antibodies to citrus red mite than in those without skin response or serum specific IgE (P < 0.05, respectively). CONCLUSION: Citrus red mite is the most important allergen in citrus farmers with asthma and rhinitis in which causative allergen has not been identified. It should be included in the skin test battery for screening the causative allergen in farmers exposed to citrus red mite.     

House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program

BACKGROUND: Children with asthma have a high prevalence of environmental allergies, especially to indoor allergens. The relationships of exposure to indoor allergens (dust mites, cat, dog, cockroach, and molds) and other host factors to allergy sensitization have not been evaluated simultaneously in a large cohort. OBJECTIVES: We studied 1041 children aged 5 to 12 years with mild-to-moderate asthma to determine risk factors associated with having positive allergy skin test responses to indoor allergens. Also, we described, compared, and contrasted 6 allergens in the home environments of these children from 8 North American cities. METHODS: Data were used from baseline visits of the Childhood Asthma Management Program. Patients' sensitivities to house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cats, dogs, cockroaches, and molds were examined for relationships to demographic variables, home dust allergen exposures, number of other positive allergy skin test responses, total serum IgE levels, and smoking in the home. RESULTS: San Diego (78.5%) and Toronto (59.3%) had the topmost percentages of homes with moderate-to-high house dust mite levels. Boston (21.5%), St Louis (16.3%), and Baltimore (13.4%) had the highest percentages of homes with detectable levels of cockroach allergen. For house dust mites, the higher the level of allergen exposure, the more likely patients were to have positive allergy skin test responses, with relative odds of 9.0 (95% confidence interval, 5.4-15.1) for those exposed to high mite levels (>10.0 microg/g dust) relative to those unexposed. Even exposure to low levels of mite allergen (0.020-2.0 microg/g) was found to be a significant risk factor for sensitization. For cockroach allergen, those with detectable home exposure were more likely to have positive skin test responses (relative odds, 2.2; 95% confidence interval, 1.3-3.8) than those with undetectable exposure. In contrast, levels of exposure to cat, dog, and mold allergens were not related to sensitization rates. For cat allergen, this may reflect lower rates of cat ownership among highly sensitized subjects. Furthermore, the number of allergy skin test responses that were positive, excluding the test for the outcome of interest for each model, and total serum IgE levels were strong independent predictors of sensitization. CONCLUSIONS: Levels of exposure determined by house dust analysis are important determinants of sensitization for dust mite and cockroach allergen. This relationship was not demonstrable for cat, dog, or mold allergens, possibly because of confounding factors. For all allergens studied, the degree of atopy, determined by the total number of positive skin test responses or by total serum IgE levels, is an important contributing risk factor for sensitization.     

Family history, dust mite exposure in early childhood, and risk for pediatric atopy and asthma

BACKGROUND: Dust mite allergen exposure is considered a major determinant of sensitization to these allergens during childhood and a risk factor for pediatric asthma. OBJECTIVE: By using a birth cohort in a setting with a substantial burden of dust mite allergen, we evaluated exposure and risk for outcomes related to allergy and asthma. METHODS: We collected dust from the bedrooms of 428 children born from 1987 to 1989 and measured Der f 1 and Der p 1 (microg/g dust, combined). Follow-up at 6 to 7 years of age included clinical examination, skin prick testing, specific serum IgE measurement, and methacholine challenge. RESULTS: No overall association was evident for any outcome except bronchial hyperresponsiveness (adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.00; P <.050; and OR, 0.53; CI, 0.27-1.04; P <.065 for dust mite allergen levels > or =2 microg/g and >10 microg/g, respectively). With a parental history of allergy and asthma, there was an association between a positive dust mite skin test (OR, 2.09; CI, 0.93-4.73; P <.076) and dust mite allergen level >10 microg/g. The inverse was true for children without a parental history. Dust mite exposure of >10 microg/g was associated with a decreased risk of current atopic asthma among children with a parental history (OR, 0.39; CI, 0.05-3.13; P <.376), but with increased risk if without a parental history (OR, 1.52; CI, 0.22-10.6; P <.673). CONCLUSION: Parental history is an important independent variable in the relationship between early dust mite exposure and atopic outcomes. Increased exposure during infancy is associated with a higher risk for sensitization in the presence of a positive parental history, but is protective among children of parents without a history of atopic disease.     

Cloning and expression of Blo t 1, a novel allergen from the dust mite Blomia tropicalis, homologous to cysteine proteases

BACKGROUND: House dust mite allergens have been shown to be a very important stimulus in the causation of asthma and triggers for the exacerbation of symptoms. Therefore, characterization of mite-derived allergens at the molecular level is an important step for the development of effective diagnostic and therapeutic approaches, as well as for epidemiological studies. OBJECTIVE: To clone, express and characterize at the molecular level the cysteine protease from Blomia tropicalis (Bt). METHODS: A full-length cDNA encoding Blo t 1 was cloned from a Bt cDNA library using a PCR and RACE-based strategy. The cDNA was PCR-amplified, sequenced and subcloned into a prokaryotic expression vector. The allergenicity of the recombinant Blo t 1 was evaluated for IgE reactivity by Western blot. RESULTS: Blo t 1 cDNA encodes a 221 amino acids polypeptide with an estimated molecular weight of 25 kDa. The recombinant protein is 35% identical to other mite cysteine proteases. Recombinant Blo t 1 (rBlo t 1) bound IgE from 62% of Bt skin test-positive serum. Dermatophagoides pteronyssinus (Dp) skin test-positive sera did not react with rBlo t 1, indicating the possible presence of unique IgE epitopes on the rBlo t 1 molecule. A three-dimensional image of Blo t 1, constructed based on predicted analysis, showed conserved secondary and tertiary structure with other cysteine proteases. CONCLUSION: We report the cloning, expression and IgE reactivity of Blo t 1, a novel allergen from the domestic mite Blomia tropicalis (Bt), highly homologous to cysteine proteases. This putative cysteine protease, designated Blo t 1, may play a major role as an immunodominant allergen involved in dust mite-specific IgE-mediated hypersensitivity.     

Molecular cloning and characterization of full-length cDNAs encoding a novel high-molecular-weight Dermatophagoides pteronyssinus mite allergen, Der p 11

BACKGROUND: Dermatophagoides pteronyssinus (Dp) and D. farinae (Df) mites are the most important source of indoor aeroallergens. Most Dp mite allergens identified to date have relatively low molecular weights (MWs). Identification of high-MW mite allergens is a crucial step in characterizing the complete spectrum of mite allergens and to provide appropriate tools for diagnostic and therapeutic application. METHODS: The full-length Der p 11 cDNA clone was isolated using cDNA library immunoscreening, the 5'-3' rapid amplification of cDNA ends (RACE) system and polymerase chain reactions (PCR). The whole cDNA insert and its PCR-derived DNA fragments (p1 to p4) were generated and expressed in the Escherichia coli expression system. The allergenicity of the recombinant protein and its peptide fragments was examined by IgE immunodot assays. The IgE-binding reactivity of rDer p 11 was analyzed in the serum of 50 asthmatic children with positive reactivity to Dp mite extract. Its recombinant peptide fragments were also examined by immunodot assays in 30 mite-allergic children. RESULTS: Der p 11 cDNA consists of a 2625-bp open reading frame encoding a 103-kDa protein with 875 amino acids. It exhibits significant homology with the paramyosin of other invertebrates. The protein sequence alignment of this newly identified Dp mite allergen (denominated as Der p 11) revealed over 89% identity with Der f 11 and Blo t 1. Among 50 Dp-sensitive asthmatic children, rDer p 11 showed positive IgE-binding reactivity to 39 patients (78%). Using immunodot assays, multiple human IgE-binding activities were demonstrated in all four fragments of Der p 11. Using immunoblot assays, the dominant IgG-binding epitope for monoclonal antibody (mAb642) was located in fragment p3 only. In immunoblot assays, cross-inhibition between rDer p 11 and rDer f 11 was up to 73-80% at concentrations of 100 microg/ml. CONCLUSIONS: This study confirms that the newly identified recombinant Der p 11 is a novel and important high-MW Dp mite allergen for asthmatic children. Our data also indicates that human IgE-binding major epitopes are scattered over the entire molecule of Der p 11.     

Comparison of antigenic and allergenic composition of two partially puriflied extracts from Dermatophagoïdes farinae and Dermatophagoïdes pteronyssinus mite cultures

Dermatophagoïdes farinae (Df 80d) and Dermatophagoïdes pteronyssinus (Dp 80d) extracts were analyzed,for their antigenic and allergenic composition by means of crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE). By CIE, II antigens could be numbered in Df 80d (Df I to Df II) and seven antigens in Dp 80d (Dp I to Dp 7). This technique allowed us also to define antigens with common as well as specific parts for the two mite species. Among the antigens of D. farinae and D. pteronyssinus, only the antigen corresponding to DO and Dp 5 seems to bear common epitopes to the two mite species, whereas Df 6 and Dp 4 appear to, bear, respectively, specific epitopes 4f each species. Moreover, Df lI appears to bear specific epitopes of D. farinae, although it shows a partial identity with Dp 7. By CRIE, on 20 mite-sensitive patients' sera, we identified, for each mite extract, the allergens responsive to human specific IgE. The allergograms show that the majority of mite-sensitive patients react with Df 11 and Df 6 and with Dp 7 and Dp 4. Tines, these antigens can be considered as major allergens. The minor allergens were also identified. None of these antigens was recognized by the control sera. Moreover, we observed that, for one antigen (antigen 5) there exist antigenic determinants common to the two species of mites toward the rabbit serum and specific allergenic determinants to the human IgE response. A significant correlation was found between the specific IgE binding in CRIE and in RAST (Spearman coefficient: “rs” = 0.61 p < 0.0l ,for Df; “rs” = 0.78 p < 0.01 for Dp).     

Characterization of Der p 21, a new important allergen derived from the gut of house dust mites

Background: The house dust mite (HDM) Dermatophagoides pteronyssinus is a major allergen source eliciting allergic asthma. The aim of the study was to identify new important HDM allergens associated with allergic asthma. Methods: A cDNA coding for a new mite allergen, designated Der p 21, was isolated using immunoglobulin E (IgE) antibodies from patients with allergic asthma out of a D. pteronyssinus expression cDNA library and expressed in Escherichia coli. Results: Circular dichroism analysis of the purified allergen showed that rDer p 21 (14 726 Da) is one of the few mite allergens with an α‐helical secondary structure. The protein exhibited high thermal stability and refolding capacity, and, as determined by small angle X‐ray scattering, formed a dimer consisting of two flat triangles. rDer p 21 bound high levels of patients’ IgE antibodies and showed high allergenic activity in basophil activation experiments. Rabbit anti‐Der p 21 IgG antibodies inhibited mite‐allergic patients’ IgE binding and allowed the ultrastructural localization of the allergen in the midgut (epithelium, lumen and faeces) of D. pteronyssinus by immunogold electron microscopy. Der p 21 revealed sequence homology with group 5 mite allergens, but IgE and IgG reactivity data and cross‐inhibition studies identified it as a new mite allergen. Conclusions: Der p 21 is a new important mite allergen which is liberated into the environment via faecal particles and hence may be associated with allergic asthma.     

Molecular mimicry as the key to the dominance of the house dust mite allergen Der p 2

Evaluation of: Trompette A, Divanovic S, Visintin A et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009).

The majority of complex sources of allergen contain a small number of dominant allergens that bind at least half of the IgE antibodies of allergic subjects. For the house dust mite Dermatophagoides pteronyssinus, these allergens are Der p 1 and Der p 2. There is evidence that the cysteine-protease activity of Der p 1 imparts adjuvant activity to the allergen. It has now been shown that Der p 2 mimics the activity of its fellow ML-domain protein, MD-2, by presenting lipopolysaccharide to Toll-like receptor-4 for the activation of inflammatory genes. In accord with this, Der p 2 presented with lipopolysaccharide also induced enhanced type 1 allergic sensitization of mice, even when they were deficient in MD-2. The mimicry of MD-2 can thus also self adjuvant Der p 2 to enhance it allergenicity. This not only describes an intriguing mechanism for enhancing allergenicity but also, since both of the dominant mite allergens have intrinsic adjuvant activity, exemplifies an important principle for driving allergic sensitization.     

Analysis of the sensitization profile towards allergens in central Africa

BACKGROUND: Almost no information is available regarding the prevalence of IgE-mediated allergies and the disease-eliciting allergens in tropical Africa. OBJECTIVE: To study IgE-mediated allergies and the allergen profile in allergic patients from Zimbabwe. METHODS: The frequency of sensitization to common environmental allergen sources was determined by skin prick testing in 650 allergic patients from Zimbabwe. Fifty representative sera were analysed for IgE reactivity to 20 respiratory and 20 food allergen extracts by multiallergen extract testing. The IgE reactivity profiles to recombinant pollen and mite allergens were compared between grass pollen- and mite-sensitized patients from Zimbabwe and central Europe. Sera from grass pollen-allergic patients were also analysed for IgE reactivity to nitrocellulose-blotted natural timothy grass and Bermuda grass pollen allergens. RESULTS: IgE-mediated allergies were found to be common in Zimbabwe. Similar to the situation in central Europe, mites and grass pollens represented the most prevalent allergen sources. However, the IgE reactivity profiles determined with single recombinant pollen and mite allergens revealed interesting differences between the European and African patients, which most likely reflect the local allergen exposure. CONCLUSIONS: The striking differences regarding sensitization to grass pollen and mite allergens between African and European patients revealed by recombinant allergen-based testing emphasize the need for component-resolved allergy testing to optimize allergy prevention and therapy in different populations.     

Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens

BACKGROUND: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. OBJECTIVE: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. METHODS: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. RESULTS: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P < .04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P = .23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P < .001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 microg/g). CONCLUSION: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.     

Buckwheat anaphylaxis: an unusual allergen in Taiwan

IgE-mediated hypersensitivity to buckwheat is common in Korea, Japan, and some other Asian countries. However, buckwheat is not a common allergen in Taiwan. We report a woman with asthma who had anaphylactic shock, generalized urticaria, and an acute exacerbation of asthma five minutes after ingesting buckwheat. The patient underwent skin prick and Pharmacia CAP testing (Uppsala, Sweden) for specific IgE to buckwheat, white sesame and soybean as well as other common allergens in Taiwan including Dermatophagoides pteronyssinus (Dp), D. farinae (Df), cat and dog dander, cockroach, egg white, cow milk and codfish. The patient had a strongly positive skin prick test response to buckwheat and positive reactions to Dp and latex. Specific IgE results were class 6 for buckwheat, class 4 for Dp and Df, and class 2 for dog dander, wheat, sesame and soybean. Results of an open food challenge with white sesame and soybean were negative. Although buckwheat is a rare allergen in Taiwan, it can cause extremely serious reactions and should be considered in patients presenting with anaphylaxis after exposure to buckwheat.     

Antigens and allergens in Dermatophagoides farinae mite: II. Purification of AG 11, a major allergen in Dermatophagoides farinae

Ammonium sulphate precipitation and DEAE chromatography is an efficient way of purifying Ag 11, the main allergen in Dermatophagoïdes farinae mites, which has already been characterized by crossed radioimmunoelectrophoresis. At 60% of saturation in ammonium sulphate, a precipitate is formed which, dissolved and dialysed has been named fraction A 60. It is mainly composed of Ag 11. In the fraction DE obtained by DEAE chromatography of the ammonium sulphate fraction A 60, Ag 11 appears homogeneous on crossed-immunoelectrophoresis. Isoelectrofocusing results indicate an average isoelectric point near neutrality in agreement with the non-absorbtion of Ag 11 on the DEAE cellulose at a weak ionic strength (0.01, at pH 7.2). By sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration Ag 11 has a molecular weight of 28,000.

Ag 11 appears as a single polypeptidic chain with numerous dithio-bonds implying a highly folded and resistant structure. Oligosaccharides could be present as constituting molecules as well as contaminating ones as was assumed for hexosamines. These results are discussed with reference to a similar study performed on the major allergen of Dermatophagoïdes pteronyssinus. The allergenic properties of Ag 11 as present in fraction DE were tested by RAST-based methods. Fraction DE is an inhibitor as good as Df 80d and when it is coated on paper discs it can bind specific IgE in sera from the majority of mite sensitive patients. The results suggest that Ag 11 is a major allergen from D. farinae.

     

The value of acoustic rhinometry in assessing nasal responses to cat exposure

Background: Acoustic rhinometry (AR) uses sonar principles to map the anatomy of the nasal cavity and has been used in other studies to assess acute airway responses to allergen exposure. Objective: The purpose of this study was to evaluate the utility of AR in assessing acute airway responses to cat allergen exposure by using a well-characterized cat exposure model. Methods: Thirty subjects with a history of cat-induced rhinitis and a positive skin prick test response to cat allergen underwent an environmental cat challenge. Of these 30 subjects, 10 also had repeat challenges at lower levels of antigen to determine whether there was a dose response. Five subjects with negative skin test responses to cat were recruited as control subjects. During the 1-hour cat exposure, upper and lower respiratory symptoms were scored every 5 minutes, and spirometry and AR were obtained every 15 minutes. Results: Although 29 of 30 subjects had changes in AR measurements, no correlations were detected between upper respiratory symptom scores and any of the changes observed in AR. In comparing the baseline challenges with lower antigen level challenges, upper respiratory symptom scores differed significantly (P = .002), whereas AR responses were nearly identical. Subjects without cat allergy did exhibit less response by AR (P = .05 to .13), but the greatest differences remained in the upper respiratory symptoms scores (P < .0001). Conclusion: We conclude that although AR does provide an objective measure of nasal response to allergen exposure, it has significant limitations. These are evidenced by the lack of correlation with symptoms, the inability to measure a dose response, and the changes noted even among the control subjects. (J Allergy Clin Immunol 1998;102:896-901).     

CpG Oligodeoxynucleotide Inhibits Cockroach-Induced Asthma via Induction of IFN-γ+ Th1 Cells or Foxp3+ Regulatory T Cells in the Lung

PurposeCpG oligodeoxynucleotide (CpG-ODN), a TLR9 agonist, activates innate immunity and induces Th1 response. Although the immune modulatory effect of CpG-ODN has been extensively studied, its function in cockroach extract-induced allergic asthma has not been studied. Here, we investigated the inhibitory function of CpG-ODN in cockroach extract-induced asthma in mice with different treatment schemes.MethodsScheme 1: BALB/C mice were intra-nasally co-administered by cockroach extract and CpG-ODN twice a week for 3 weeks; Scheme 2: The mice were intra-nasally pre-treated with CpG-ODN at day 0 and cockroach allergen challenge was performed from day 3 as in scheme 1. Scheme 3: Cockroach allergen challenge was performed as in scheme 1 and CpG-ODN was post-treated at day 21. Then, BAL cell count, flow cytometric analysis of alveolar macrophages, regulatory T cells, and lung tissue histology, Th1 and Th2 cytokines, serum IgE, cockroach specific IgE, IgG1/IgG2a ratio, and airway hyper-responsiveness were evaluated.ResultsMice with repeated intra-nasal exposure to CpG-ODN showed a dramatic decrease in eosinophilic inflammation, goblet cell hyperplasia, and airway hyper-responsiveness with reduction of IL-13, IL-5, and serum IgE, cockroach specific IgE and IgG1/IgG2a ratio. This inhibitory function might be related to the up-regulation of IL-10 and CD4⁺Foxp3⁺ regulatory T cells in the lung. Interestingly, one-time challenge of CpG-ODN either prior or posterior to cockroach extract exposure could modulate airway inflammation and hyper-responsiveness via increase of Th1 response.ConclusionsCollectively, our data suggest that CpG-ODN treatment modulates Th2 inflammation in the lung by induction of regulatory T cells or Th1 response in a cockroach-induced asthma model.