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PubMed2004

Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy.

BACKGROUND: The efficacy and safety of sublingual immunotherapy (SLIT) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial. METHODS: After application of an anti-mite mattress cover, patients were only included in the study when the cumulative symptom score over a fortnight was greater than 70 out of a possible total of 168. Thirty-two of the 120 patients selected were randomized to receive SLIT for 2 years: 17 received placebo and 15 received the Dermatophagoides pteronyssinus and D. farinae 50/50 allergen extract. RESULTS: Significant between-group differences were observed after 1 year and persisted at the end of the second year for the rhinitis total score (P < 0.02), blocked nose score (P < 0.01) and nasal itching score (P < 0.01). Skin reactivity to house dust mites was significantly reduced in the group receiving house dust mite extract (P < 0.03). No statistical difference was observed between the two groups for medication scores, but a low medication consumption was observed in all patients. No serious and no systemic adverse reactions were reported. CONCLUSION: This study indicates the superiority of active treatment vs. placebo, evaluated on efficacy criteria (rhinitis score) or objective criteria (skin reactivity). The availability of a solid form (tablet) could represent a progress in terms of patient acceptability.

Administration, Sublingual↗
PubMed1996

Mite allergy, clinical atopy, and restriction by HLA class II immune response genes.

From a community-based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA-class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non-mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence-specific oligonucleotide typing with PCR-amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite-sensitized children and one of the other two groups. However, the presence of certain DRB- and DPB-haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < or = 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/ *0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < or = 0.01). Thus, our findings do not suggest a relevance of HLA-class II molecules to mite allergy; however, some HLA class II haplotypes appear to be predictive of the incidence of atopic disorders.

Allergens↗
PubMed1996

Childhood asthma and exposure to indoor allergens: low mite levels are associated with sensitivity.

The prevalence and level of sensitivity to indoor allergens were studied in relation to current exposure at home in 124 children with perennial asthma living in three climatic zones of Sweden. The house dust mite (HDM) allergen levels were higher in the South than in the North (p < 0.001), while cat and dog allergen levels tended to be higher in the North than the South (n.s.). Thirty-four percent of the children were sensitive to the HDM Dermatophagoides pteronyssinus, as determined by IgE antibodies in vitro, 27% were sensitive to D. farinae, 57% to cat and 55% to dog. Sensitivity to HDM was significantly more prevalent in Southern, than in Central and Northern Sweden (p = 0.001) where the children were more often sensitive to pets (cat p = 0.005, dog p = 0.002). A significant association between the concentration of Der p I and Der fI in the house dust and both the prevalence of sensitivity to HDM and the IgE antibody levels against mites was found even at concentrations well below the commonly suggested risk level for sensitisation of 2 micrograms/g dust. No relationship was found between pet allergen concentration in the home dust and sensitivity to pets, possibly because of exposure outside home, e.g. in schools and meeting places for leisure activities. Similarly, there was no consistent association between the level of mite or pet allergen exposure at home and asthma severity as judged by symptom and medication score. The study indicates that there is no threshold value for sensitisation to mite allergens in asthmatic children, and therefore, dust allergen levels at home should be kept as low as possible in homes of children at risk for asthma.

Adolescent↗
PubMed1996

Are combinations of questions better than individual questions for detecting sensitization to mite allergen?

Previous studies have found that questions are considerably less sensitive for predicting sensitization to dust mites than to pollens or to household pets. We studied 1160 children with respiratory symptoms to find whether the sensitivity for predicting mite allergy could be increased by asking several rather than single questions. Parents accompanying the children were asked standardized validated questions. Of the four individual questions relevant to mites, the one with the highest sensitivity for predicting a positive skin prick test to this allergen was whether the symptoms were worse when the house was being swept, vacuumed or dusted (29.8%). If an affirmative answer to that question, or to any of the other three questions, was taken as predictive of sensitization, the sensitivity increased to 54.2%. However, requiring only a single affirmative answer to this combination of questions decreased the specificity. The sensitivity of the combination of questions was comparable to that of questions for predicting positive tests to tree pollens (56.4%), cats (56.4%), grass pollens (52.5%) and dogs (51.4%). We conclude that asking a combination of questions is an useful for indicating possible sensitization to dust mite as are questions for detecting sensitization to other common inhalant allergens.

Adolescent↗
PubMed2006

No evidence for the 'Meselson effect' in parthenogenetic oribatid mites (Oribatida, Acari).

It has been hypothesized that in ancient apomictic, nonrecombining lineages the two alleles of a single copy gene will become highly divergent as a result of the independent accumulation of mutations (Meselson effect). We used a partial sequence of the elongation factor-1alpha (ef-1alpha) and the heat shock protein 82 (hsp82) genes to test this hypothesis for putative ancient parthenogenetic oribatid mite lineages. In addition, we tested if the hsp82 gene is fully transcribed by sequencing the cDNA and we also tested if there is evidence for recombination and gene conversion in sexual and parthenogenetic oribatid mite species. The average maximum intra-specific divergence in the ef-1alpha was 2.7% in three parthenogenetic species and 8.6% in three sexual species; the average maximum intra-individual genetic divergence was 0.9% in the parthenogenetic and 6.0% in the sexual species. In the hsp82 gene the average maximum intra-individual genetic divergence in the sexual species Steganacarus magnus and in the parthenogenetic species Platynothrus peltifer was 1.1% and 1.2%, respectively. None of the differences were statistically significant. The cDNA data indicated that the hsp82 sequence is transcribed and intron-free. Likelihood permutation tests indicate that ef-1alpha has undergone recombination in all three studied sexual species and gene conversion in two of the sexual species, but neither process has occurred in any of the parthenogenetic species. No evidence for recombination or gene conversion was found for sexual or parthenogenetic oribatid mite species in the hsp 82 gene. There appears to be no Meselson effect in parthenogenetic oribatid mite species. Presumably, their low genetic divergence is due to automixis, other homogenizing mechanisms or strong selection to keep both the ef-1alpha and the hsp82 gene functioning.

Animals↗
PubMed1996

Effects of an acaricide on mite allergen levels in the homes of asthmatic children.

Previous study by the current authors has shown that treating homes with D'Allergen, an acaricidal agent, can reduce bronchial hyper-reactivity in asthmatic children with house dust mite allergy. In the present study, the effects of a single D'Allergen treatment on the levels of major dust mite allergens, Der p I and Der f I was evaluated, and the duration of its effectiveness in the environment determined. Twenty randomly selected homes were treated with the acaricide and ten remained untreated. Dust samples were collected from mattresses, upholstered sofas and carpets of these homes before and 1, 2 and 4 months after treatment. The samples were then assayed for Der p I and Der f I allergens using a sandwich enzyme immunoassay. The results showed that D'Allergen was effective in reducing dust mite allergen levels in all three niches by 1.5-22.3 times below baseline values. This effect, however, was only present for 2 months, and the dust mite allergen levels increased to those of the baseline by the fourth month after treatment. These results indicated that repeated applications of the acaricide were required at 2-3 monthly intervals to obtain optimal effectiveness.

Air Pollution, Indoor↗
PubMed1994

Asthma severity and morbidity in a population sample of Sydney schoolchildren: Part II--Importance of house dust mite allergens.

BACKGROUND: Despite an increasing prevalence of childhood asthma, few studies have quantified the strength of associations between asthma and its aetiological factors. AIMS: To quantify the risk factors associated with childhood asthma and to investigate the characteristics of children most at risk. METHODS: We studied a population sample of 1339 schoolchildren aged eight-11 years living in Sydney, NSW. Questionnaires were used to measure respiratory illness, histamine inhalation test to measure airway hyperresponsiveness (AHR), skin prick tests to measure atopy and ELISA assay to measure house dust mite allergen (Der p I) levels. 'Current asthma' was defined as the presence of wheeze in the previous year and AHR. RESULTS: The mean Der p I level in 72 homes was 22.5 micrograms/gm dust which is high compared to suggested thresholds of 2 microgram/gm for sensitisation and 10 micrograms/gm for exacerbation of symptoms. Sensitisation to house dust mites was the most important risk factor for current asthma (odds ratio 7.0, 95% CI 9.4, 22.2). Sensitisation to ryegrass was of minor importance (odds ratio 2.0, 95% CI 1.4, 3.1). The presence of AHR was strongly related to the degree of sensitisation to house dust mite allergen and children with skin wheals greater than 4 mm had frequent morbidity caused by asthma. CONCLUSIONS: To reduce the high prevalence of childhood asthma in NSW, it is imperative that we design interventions which recognise that house dust mite allergens are a dominant risk factor and that children with large skin wheal reactions to this allergen are most at risk for severe illness including disturbed sleep, days missed from school and urgent medical attention.

Airway Resistance↗
PubMed1995

Modulation of mite antigen-induced immune responses by lecithin-bound iodine in peripheral blood lymphocytes from patients with bronchial asthma.

1. Dermatophagoides farinae (Df) mite antigen induced IgE synthesis associated with an imbalance of cytokine production in mite-sensitive patients with bronchial asthma; increased production of interleukin 4 (IL-4), and decreased production of interferon-gamma (IFN-gamma) was specifically induced in these patients' lymphocytes. 2. Lecithin-bound iodine (LBI), with which children with bronchial asthma have been successfully treated in the range of 0.5 to 5 microM, concentrations comparable to LBI blood levels in medicated individuals, modified mite antigen-induced immune responses, thereby decreasing abnormal lymphocyte functions. 3. In Df antigen-driven immune responses, inhibition of IgE generation accompanied by suppression of IL-4 and the recovery of IFN-gamma production was successful when LBI was used in vitro. 4. LBI also acted on normal PBMCs by downregulating the IL-4-induced IgE synthesis, phytohaemagglutin (PHA)- and phorbol myristate acetate (PMA) plus calcium ionophore (CaI)-induced IL-4 secretion, and by upregulating purified protein derivatives (PPD)-induced IFN-gamma production. Therefore, LBI was capable of inhibiting the IgE and IL-4 responses and of enhancing IFN-gamma production both from allergen-stimulated atopic cells and from non-atopic cells appropriately stimulated. 5. The expression of human histocompatibility leukocyte antigen (HLA), class II antigens and intercellular adhesion molecule 1 (ICAM-1) on monocytes, crucial molecules for T cell-monocyte interactions, was not altered by LBI. 6. LBI probably acts as an immunomodulator to ameliorate mite antigen-induced abnormal cell-mediated immune responses in patients with bronchial asthma caused by Df antigen thereby leading to improvement of their clinical status.

Animals↗
PubMed1995

Nitric oxide metabolites in nasal lavage fluid of patients with house dust mite allergy.

BACKGROUND: The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined. METHODS: Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house dust mite. In a double blind placebo controlled crossover study fluticasone propionate 200 micrograms aqueous nasal spray was administered twice daily for two weeks. In response to provocation with house dust mite extract (after four basal nasal lavages) nasal lavages were performed every hour for 9.5 hours by washing the nose with saline. In addition, a similar lavage protocol was performed in healthy volunteers with or without challenge with phosphate buffered saline. RESULTS: Nitric oxide is present in nasal lavage fluid in detectable amounts (range 10-50 microM), the level gradually increasing with time in both patients and controls after a decrease during the four basal lavages. Treatment with fluticasone propionate aqueous nasal spray did not affect initial basal production of nitric oxide nor production following provocation with house dust mite extract. CONCLUSIONS: Production of nitric oxide in nasal mucosa determined in sequential nasal washings is not affected by therapeutic doses of intranasal steroids.

Administration, Intranasal↗
PubMed1998

IgE binding capacity of synthetic and recombinant peptides of the major storage mite (Lepidoglyphus destructor) allergen, Lep d 2.

BACKGROUND: Lepidoglyphus destructor is an important non-pyroglyphid mite species in Europe and a dominant allergen in farming environments. The major allergen of L. destructor, Lep d 2, is a protein of 13.2 kD that is recognised by about 90% of sera RAST positive to this mite species. METHODS: The cDNA of two isoallergens of the Lep d 2 has previously been sequenced and the protein expressed in different protein expression systems. In order to map the B-cell epitopes, the full length protein and the truncated forms of the protein have been expressed in Escherichia coli as glutathione-S-transferase (GST) fusion proteins. Recombinant Lep d 2 fragments and synthetic overlapping 15 mer peptides spanning Lep d 2 were probed with sera from patients allergic to storage mite. RESULTS: The full-length (125 amino acids) GST fusion protein reacted strongly with patient IgE in Western blots and dot blots. Synthetic peptides failed to react with IgE antibodies from mite-allergic patients and the truncated fusion proteins displayed weak IgE-binding capacity. CONCLUSION: We conclude that there are no dominant linear IgE-binding epitopes in Lep d 2. Recombinant or synthetic Lep d 2 fragments may, however, be further evaluated as hypoallergenic candidate molecules for specific immunotherapy.

Allergens↗
PubMed2003

Cloning and characterisation of two IgE-binding proteins, homologous to tropomyosin and alpha-tubulin, from the mite Lepidoglyphus destructor.

BACKGROUND: The dust mite Lepidoglyphus destructor is a major source of mite allergy in European rural environments, but it also causes allergy in urban populations around the world. We have previously cloned, sequenced and expressed several allergens from L. destructor (Lep d 2, Lep d 5, Lep d 7 and Lep d 13). The aim of this study was to identify and clone additional allergens from L. destructor, and to evaluate their IgE-binding reactivities. METHODS: PCR and screening with sera from L. destructor-sensitised individuals were used to isolate new clones from a phage display L. destructor cDNA library. The complete coding sequences of the clones were determined and expressed as His(6)-tagged recombinant proteins in Escherichia coli. The recombinant proteins were analysed by SDS-PAGE, immunoblotting and mass spectrometry. RESULTS: Two new clones, showing homology to tropomyosin and alpha-tubulin in several species, were isolated from the phage display L. destructor cDNA library. Due to its homology to group 10 dust mite allergens, the tropomyosin clone was named Lep d 10. The IgE-binding frequencies of the recombinant Lep d 10 and alpha-tubulin were 13% (18/136) and 12% (11/95), respectively, among subjects with IgE reactivity to mites and/or crustaceans. CONCLUSIONS: Two new allergens from L. destructor have been identified and can now be added to the repertoire of recombinant L. destructor allergens. In addition, both these allergens belong to highly conserved protein families and may be important for evaluation of allergenic cross-reactivity.

Allergens↗
PubMed2003

Gene expression analysis of atopic dermatitis-like skin lesions induced in NC/Nga mice by mite antigen stimulation under specific pathogen-free conditions.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammation characterized by pruritic and eczematous skin lesions usually observed in patients with a familial history of atopic diseases, but its exact etiology is unclear. An animal model is indispensable for the analysis of the pathogenesis and the development of new drugs to treat this disease. Here, we compare changes in gene expression profiles in the AD-like skin lesions of NC/Nga or BALB/c mice stimulated intradermally by mite antigen under specific pathogen-free (SPF) conditions. METHODS: Mite Extract-Dp was injected intradermally into the right and left pinnae and into the skin of the back of NC/Nga or BALB/c mice in 2 places once per 3 days, and the clinical symptoms and the ear thickness were measured. On day 14 or day 28 after starting mite extract injection, we collected plasma and pinnae from NC/Nga or BALB/c mice. The amount of total immunoglobulin E (IgE) in plasma was assayed. We analyzed mRNA transcripts in pinnae using real-time quantitative PCR for the murine counterparts of several known allergy-related genes. Moreover, genome-wide gene expression in pinnae from NC/Nga mice was analyzed using high-density oligonucleotide arrays (GeneChip, Affymetrix). RESULTS: From 2 weeks after stimulation, marked skin inflammation was induced in the pinnae of NC/Nga but not BALB/c mice. However, IgE levels in sera rose equally in both strains. Quantitative PCR analysis and comprehensive GeneChip analysis of the AD-like pinna skin lesions revealed that their development was accompanied by changes in expression of more than 1,000 genes. These included cytokines, cytokine receptors, proteases, and adhesion molecules. Furthermore, genes thus far not reported in association with AD were also affected. CONCLUSION: From these results, the NC/Nga mouse model using mite sensitization under SPF conditions could be useful for elucidating the mechanisms of AD pathogenesis and developing more effective therapy for AD.

Animals↗
PubMed1981

House dust mite hypersensitivity: morning dipping and severity of wheeze.

Atopic subjects with asthma are frequently hypersensitive to house dust mite (Dermatophagiodes pyteronyssinus). Exaggerated nocturnal or early morning wheezing might occur in these patients, because of exposure to the allergen during the night, particularly in view of the biphasic response that it produces in airway resistance. This might be of diagnostic value in determining the relevance of house dust mite to the asthma of a particular subject. This hypothesis was tested in 100 patients with diurnal variation in airway obstruction, 78 of whom were predominantly asthmatic. Hypersensitivity to house dust mite was measured by a simple prick test. Morning dipping was seen in patients without hypersensitivity to house dust mite. There was no significant quantitative relationship between morning dip and hypersensitivity. There was a significant relationship between morning dip and severity of wheeze. This study confirms the view that morning dipping is a reflection of the severity of asthma, rather than a feature of any particular type.

Adult↗
PubMed1977

Characterization of the allergenic components of the house dust mite, Dermatophagoides farinae.

Characterization and purification of the allergenic components of the house dust mite, Dermatophagoides farinae, were investigated. It was found that the mite antigen was heat-stable, pronase-sensitive, and periodate-resistant, which suggested that the antigenic determinants of the mite antigen resided mainly in the protein component. Purification of the mite antigen was tried using Sephadex G-150, DEAE cellulose, and isoelectrofocusing columns. The most potent allergenic fraction was around 20,000-30,000 in molecular weight, although the allergenic activity spread in a wide molecular weight range. Prausnitz-Küstner type skin reactions were performed on rats using mouse homocytotropic antibodies for allergenic evaluation, and the clinical usefulness of this method is discussed.

Allergens↗
PubMed1990

Bronchial responsiveness to mite allergen in atopic dermatitis without asthma.

Eight patients with atopic dermatitis (AD) without a history of asthmatic episodes and 8 patients with mite-allergic bronchial asthma (BA) were subjected to bronchial inhalation challenge with a nonspecific stimulus (acetylcholine) and an immunologically specific stimulus (house dust mite allergen). AD patients had a significantly greater concentration of IgE (p less than 0.01) and antimite IgE antibody (p less than 0.05) than BA patients. Nonspecific bronchial hyperreactivities of AD patients distributed from normal to asthmatic range. After allergen challenge, all 8 AD patients and all 8 BA patients showed an immediate asthmatic response (IAR). The mite extract concentration to induce an IAR was significantly (p less than 0.01) greater in AD patients than in BA patients. A late asthmatic response was observed in 6 out of 8 BA patients, whereas it was not observed in any AD patient. Our results showed that AD patients are less reactive to a specific mite allergen than BA patients in spite of greater concentrations of antimite IgE antibody. They suggest that this difference in the bronchial reactivity to the allergen concerns the difference in the onset of clinical symptoms and that a certain level of bronchial hyperreactivity to the allergen is a prerequisite for the development of asthmatic symptoms.

Adolescent↗
PubMed1996

Systemic anaphylaxis after eating storage-mite-contaminated food.

We describe 2 cases in whom systemic anaphylaxis developed shortly after they had eaten food contaminated by a storage mite, Tyrophagus putrescentiae. We were able to demonstrate that these cases were sensitive to the storage mites but not to food allergens, leading us to conclude that the cases' anaphylactic episodes were the result of ingestion of the storage mites. This is the first report of the ingestion of storage mites causing systemic anaphylaxis in sensitive persons.

Adolescent↗
PubMed1996

Cetirizine reduces ICAM-I on epithelial cells during nasal minimal persistent inflammation in asymptomatic children with mite-allergic asthma.

It has been recently demonstrated that individuals who suffer from mite allergy present mucosal inflammation even when asymptomatic. This situation is characterized by infiltration of inflammatory cells (eosinophils and neutrophils) and by ICAM-I expression on epithelial cells. It has been called 'minimal persistent inflammation' (MPI) for its relationship with natural exposure to allergen, which is continuous in the case of mite allergy. ICAM-I (or CD54) expression on epithelial cells is relevant for several reasons: (a) healthy individuals and patients with pollen allergy out of the pollen season do not express this molecule; (b) ICAM-I is the natural ligand of LFA-1 (an integrin expressed on granulocytes), and (c) ICAM-I is also receptor for rhinoviruses. It is well known that viral infections precede asthmatic attacks; consequently, this correlation is more frequent in cases of mite allergy. Cetirizine is an antiallergic drug that can reduce both inflammatory infiltrate and ICAM-I expression induced by allergen-specific conjunctival challenge. The aim of this study was to evaluate the effect of cetirizine on MPI in 20 children (5-14 years old) with mite allergy. All the children suffered from mild asthma and 9 also had rhinitis (they had been asymptomatic, and thus not treated, for 2 months). The study was double-blind, placebo controlled and randomized and children took Cetirizine or placebo for 15 days. At the beginning and end of the study, nasal scrapings were performed to evaluate inflammatory cell infiltration (eosinophils and neutrophils) and ICAM-I expression on epithelial cells. Cetirizine-treated children showed a significant reduction (or even total absence) of ICAM-I expression on epithelial cells (p less than 0.002) and a reduction trend in inflammatory cell counts compared with placebo. In conclusion, Cetirizine might be envisaged as fruitful for the prolonged treatment of allergic children, including during clinical latency, to prevent possible relapse or rhinovirus infections.

Adolescent↗
PubMed1996

Chronologic analysis of eosinophil granule protein deposition and cell adhesion molecule expression in mite allergen-induced dermatitis in atopic subjects.

To investigate the process of eosinophil recruitment in atopic dermatitis (AD), patch testing with crude dust-mite allergens was performed on normal-appearing skin of 9 adult AD patients with high levels of mite-specific IgE antibodies. Positive reactions were observed in 6 AD subjects, whereas 0 of 7 control subjects showed positive reactions to mite allergens. Positive reaction sites were biopsied chronologically and studied histologically and immunohistochemically. Eosinophils were seen in postcapillary venules in the dermis at 2 h, followed by infiltration of eosinophils at 6 h which peaked at 24 and 48 h. In the epidermis, eosinophilic spongiosis was seen at 48 h. Positive reactions against eosinophil granule proteins were observed in connective tissues as well as on eosinophils. Almost all infiltrating eosinophils were positive for BMK-13 (an antibody against major basic protein); half of them were positive for EG2 (an antibody against eosinophil cationic protein). With regard to adhesion molecules, expression of E-selectin and intercellular adhesion molecule-1 endothelial cells was up-regulated as infiltrating eosinophils increased in number. These findings suggest that eosinophil transmigration from endothelial cells and eosinophil degranulation play important roles in initiating early AD lesions induced by transepidermal mite allergen permeation.

Adult↗