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House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study.

BACKGROUND: The safety and the efficacy of sublingual-swallow immunotherapy (SLIT) in perennial conjunctivitis caused by house dust mite were evaluated in a double-blind, placebo-controlled study including 60 patients for 24 months. METHODS: Patients received either placebo or SLIT with standardized Dermatophagoides pteronyssinus (D.pt.) and D. farinae (D.f.) 50/50 extract. The evaluation of the efficacy of the SLIT was obtained by using standardized D. pteronyssinus (D.pt.) extracts on the antigen-specific conjunctival provocation test (CPT). Specific CPT, skin sensitivity and serum-specific IgE were performed before starting treatment and 6, 12, 18 and 24 months. RESULTS: Of the 60 patients included, only 45 completed the study (26 in the active group and 19 in the placebo group, P < 0.05). Two out of 30 (6.6%) patients dropped out because of insufficient efficacy in the active group compared to eight out of 30 (26.6%) in the placebo group (P < 0.05). There was a significant increase in the antigen threshold required to obtain a positive CPT from 8.2 IR [95% confidence interval (CI) 5.9-11.4] at baseline to 21.7 IR (95% CI 15.4-30.4) at 2 years (M24) in the active group, compared to 8.1 IR (95% CI 5.4-12.1) at baseline to 8.1 IR (95% CI 5.1-12.4) at M24 in the placebo group (P < 0.04 for overall treatment difference, P < 10-7 for the time-treatment interaction; repeated measures ANOVA). Differences between groups at individual time points were significant from 18 months on. Despite increased antigen concentrations, CPT scores were lower overall in the active than in the placebo group (P < 0.001). No serious adverse effects were reported. CONCLUSION: SLIT effectively increased the antigenic threshold required to obtain a positive CPT to house-dust mite antigen. Tolerance to and innocuity of SLIT were comparable to previous studies. This could justify recommending SLIT for the preventive treatment of perennial conjunctivitis caused by house dust mites.

Adolescent↗

Presence of miniature inverted-repeat transposable elements (MITEs) in the genome of Arabidopsis thaliana: characterisation of the Emigrant family of elements.

Although the genome of Arabidopsis thaliana has a small amount of repetitive DNA, it contains representatives of most classes of mobile elements. However, to date, no miniature inverted-repeat transposable element (MITE) has been described in this plant. Here, we describe a new family of repeated sequences that we have named Emigrant, which are dispersed in the genome of Arabidopsis and fulfil all the requirements of MITEs. These sequences are short, AT-rich, have terminal inverted repeats (TIRs), and do not seem to have any coding capacity. Evidence for the mobility of Emigrant elements has been obtained from the absence of one of these elements in a specific Arabidopsis ecotype. Emigrant is also present in the genome of different Brassicae and its TIRs are 74% identical to those of Wujin elements, a recently described family of MITEs from the yellow fever mosquito Aedes aegypti.

Arabidopsis↗

The MITE family heartbreaker (Hbr): molecular markers in maize.

Transposable elements are ubiquitous in plant genomes, where they frequently comprise the majority of genomic DNA. The maize genome, which is believed to be structurally representative of large plant genomes, contains single genes or small gene islands interspersed with much longer blocks of retrotransposons. Given this organization, it would be desirable to identify molecular markers preferentially located in genic regions. In this report, the features of a newly described family of miniature inverted repeat transposable elements (MITEs) (called Heartbreaker), including high copy number and polymorphism, stability, and preference for genic regions, have been exploited in the development of a class of molecular markers for maize. To this end, a modification of the AFLP procedure called transposon display was used to generate and display hundreds of genomic fragments anchored in Hbr elements. An average of 52 markers were amplified for each primer combination tested. In all, 213 polymorphic fragments were reliably scored and mapped in 100 recombinant inbred lines derived from a cross between the maize inbreds B73 x Mo17. In this mapping population, Hbr markers are distributed evenly across the 10 maize chromosomes. This procedure should be of general use in the development of markers for other MITE families in maize and in other plant and animal species where MITEs have been identified.

Base Sequence↗

The squamous cell carcinoma antigen 2 inhibits the cysteine proteinase activity of a major mite allergen, Der p 1.

The squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 belong to the ovalbumin-serpin family. Although SCCA1 and SCCA2 are closely homologous, these two molecules have distinct properties; SCCA1 inhibits cysteine proteinases such as cathepsin K, L, and S, whereas SCCA2 inhibits serine proteinases such as cathepsin G and human mast cell chymase. Although several intrinsic target proteinases for SCCA1 and SCCA2 have been found, the biological roles of SCCA1 and SCCA2 remain unknown. A mite allergen, Der p 1, is one of the most immunodominant allergens and also acts as a cysteine proteinase probably involved in the pathogenesis of allergic diseases. We have recently shown that both SCCA1 and SCCA2 are induced by two related Th2-type cytokines, IL-4 and IL-13, in bronchial epithelial cells and that SCCA expression is augmented in bronchial asthma patients. In this study, we explored the possibility that SCCA proteins target Der p 1, and it turned out that SCCA2, but not SCCA1, inhibited the catalytic activities of Der p 1. We furthermore analyzed the inhibitory mechanism of SCCA2 on Der p 1. SCCA2 contributed the suicide substrate-like mechanism without formation of a covalent complex, causing irreversible impairment of the catalytic activity of Der p 1, as SCCA1 does on papain. In addition, resistance to cleavage by Der p 1 also contributed to the inhibitory mechanism of SCCA2. These results suggest that SCCA2 acts as a cross-class serpin targeting an extrinsic cysteine proteinase derived from house dust mites and that it may have a protective role against biological reactions caused by mites.

Allergens↗

Effect of floorcovering construction on content and vertical distribution of house dust mite allergen, Der p I.

Domestic floorcoverings often contain appreciable quantities of particulate pollutants, such as house dust mite allergen, Der p I. Exposure to Der p I is a risk factor for the development of mite sensitization and asthma. We investigated whether carpet construction was related to the Der p I content in normal use, and its vertical distribution. We hoped to inform development of methods to remove such material. Along with one hard flooring surface, a range of carpets with differing pile conformations (loop vs. cut), pile heights, yarn twists, and pile densities were placed in houses for 13 months. The carpets were later sectioned to allow profiling of Der p I throughout the pile strata using monoclonal antibody, enzyme-linked immunosorbent assay. Not surprisingly, significantly lower amounts of Der p I were found on hard flooring than any of the carpets, which all contained similar amounts of mite allergen. For all carpets, the Der p I concentration per unit area was found to be inversely related to the distance from the carpet backing. We conclude that carpet construction is not a good predictor of Der p I content in the home. We also suggest that, as carpet construction likely influences ease of disturbance of material within the pile, methods to remove or denature particulate pollutants such as Der p I will be most effective if they are able to target the bulk of allergenic material, found toward the base of the pile.

Air Movements↗

Impact of twospotted spider mite (Acari: Tetranychidae) on growth and productivity of glasshouse cucumbers.

Experiments were conducted to assess the damage of the glasshouse cucumber by twospotted spider mite, Tetranychus urticae Koch, and to investigate when the economic yield begins to decrease after T. urticae infestations. To assess the damage, dry matter partitioning in the cucumber plant was quantified and plant growth analyses were conducted at four different T. urticae infestation levels. T. urticae infestations decreased leaf productivity by reducing the total number of leaves per plant. Approximately 14% reductions of total leaf areas could result in significant yield loss. The decreased leaf productivity by T. urticae feeding caused biomass reductions and altered the pattern of dry matter partitioning in the plant; damaged plants accumulated more dry matter in the leaf, and partitioning of dry matter to fruits was hindered. The economic yield of cucumber began to significantly decrease as early as 4 wk after heavy mite infestations. This study also showed the seasonal differences in T. urticae-cucumber damage interactions among mite infestation levels.

Agriculture↗

Genome-wide analysis of the Emigrant family of MITEs of Arabidopsis thaliana.

Miniature inverted-repeat transposable elements (MITEs) are structurally similar to defective class II elements, but their high copy number and the size and sequence conservation of most MITE families suggest that they can be amplified by a replicative mechanism. Here we present a genome-wide analysis of the Emigrant family of MITEs from Arabidopsis thaliana. In order to be able to detect divergent ancient copies, and low copy number subfamilies with a different internal sequence we have developed a computer program to look for Emigrant elements based solely on the terminal inverted-repeat sequence. We have detected 151 Emigrant elements of different subfamilies. Our results show that different bursts of amplification, probably of few active, or master, elements, have occurred at different times during Arabidopsis evolution. The analysis of the insertion sites of the Emigrant elements shows that recently inserted Emigrant elements tend to be located far from open reading frames, whereas more ancient Emigrant subfamilies are preferentially found associated to genes.

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of Der f 2, a potent allergen derived from the house dust mite (Dermatophagoides farinae).

Although a number of allergens have been identified and isolated, the underlying molecular basis for the potent immune response is poorly understood. House dust mites (Dermatophagoides sp.) are ubiquitous contributors to atopy in developed countries. The rhinitis, dermatitis and asthma associated with allergic reactions to these arthropods are frequently caused by relatively small (125-129 amino acids) mite proteins of unknown biological function. Der f 2, a major allergen from the mite D. farinae, has been recombinantly expressed, characterized and crystallized. The crystals belong to the tetragonal space group I4(1)22, with unit-cell parameters a = b = 95.2, c = 103.3 A. An essentially complete (97.2%) data set has been collected to 2.4 A at a synchrotron source. Attempts to solve the crystal structure of Der f 2 by molecular replacement using the NMR coordinates for either Der f 2 or Der p 2 (the homologous protein from D. pteronyssinus) failed, but preliminary searches using the crystalline Der p 2 atomic coordinates appear to be promising.

Allergens↗

Acaricidal activity of aqueous extracts of camomile flowers, Matricaria chamomilla, against the mite Psoroptes cuniculi.

Arcaricidal properties of decoctions, infusions and macerates of dried flower heads of camomile, Matricaria chamomilla L. (Asterales: Asteraceae) were tested in vitro against the mite Psoroptes cuniculi Delafond (Parasitiformes: Psoroptidae). This mite species is responsible for otoacariasis in domestic animals. Mites were exposed to the extracts for 24, 48 or 72 h. All the extracts tested showed highly significant acaricidal activity when compared with controls. Among them, a decoction of 10% was the only formulation which gave 100% activity at all the three observations times.

Animals↗

Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study -- 24 months results of the Study of Prevention of Allergy in Children in Europe.

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

Allergens↗

Harvest mites--a present from the Lake District.

A case of harvest-mite infestation acquired in the South Lakeland area is described in a 7-year-old boy and his immediate family. The characteristic papular urticarial lesions produced are extremely florid and may cause diagnostic problems when patients present in areas where the mite is uncommon. The life cycle of the harvest mite is discussed and recommendations for treatment given.

Animals↗

Does guanine concentration in house-dust samples reflect house-dust mite exposure?

Using specific ELISA extracts, we analyzed samples of pure mite cultures and house dust for group I allergens from Dermatophagoides pteronyssinus, D. farinae, and D. microceras. Correspondingly, we measured the concentration of guanine and xanthine by rigorous chemical methods. The pure mite cultures were used to correlate allergen levels with guanine levels. The house-dust samples one-sidedly contained more guanine than expected. This suggests that considerable amounts of guanine originate from non-house-dust mite sources and implies that guanine quantifications are of limited clinical value.

Allergens↗

Allergenic composition of the mite Suidasia medanensis and cross-reactivity with Blomia tropicalis.

BACKGROUND: Mites of the genus Suidasia are commonly found in house dust and may play an allergenic role in exposed populations. However, the allergenic potential and clinical impact of this genus has not been well established. The main objective of this project was to evaluate the allergenic role of the mite Suidasia medanensis. METHODS: An extract of S. medanensis was prepared and the allergen composition determined by immunoblot. Specific IgE antibody levels to S. medanensis and Blomia tropicalis were evaluated by radioallergosorbent (RAST) in the sera of 97 allergic asthmatic patients and 50 nonallergic subjects. Cross-reactivity between S. medanensis and the mite species B. tropicalis and Dermatophagoides farinae was investigated by RAST and immunoblot inhibitions. RESULTS: Seventy-one asthmatic patients sera (73.2%) had positive IgE reactivity to S. medanensis; 14 allergens with molecular weights ranging from 7.5 to 105 kDa were detected. The most frequently detected had molecular weights of 30-31 (54.8%), 24.5 (42%), 21 (38.7%), 47 (35%) and 58 kDa (35.5%). Blomia tropicalis extract inhibited IgE binding to nine of these identified allergens. Four B. tropicalis allergens were inhibited by S. medanensis extract. RAST inhibition results demonstrated a high degree of inhibition by B. tropicalis (87.2%) and D. farinae (90.9%) than by S. medanensis (32%). CONCLUSIONS: Sensitization to S. medanensis is common in asthmatic allergy patients in Cartagena. An important degree of cross-reactivity was established between S. medanensis and B. tropicalis, and D. farinae.

Animals↗

Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites.

BACKGROUND: The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial. METHODS: The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well. RESULTS: Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%). CONCLUSIONS: Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease.

Administration, Sublingual↗

Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy.

Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.

Administration, Sublingual↗

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study.

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.

Administration, Sublingual↗

Photoperiodic time measurement and related physiological mechanisms in insects and mites.

For over 60 years, many species of insects and mites have been known to respond in an adaptive way to seasonal changes in daylength. Responses to photoperiod allow them to survive periods of unfavorable environmental conditions. Since the early 1950s, light-sensitive and temperature-compensated circadian clocks have also been known to regulate the timing of many events (behavioral, physiological, biochemical) in all eukaryotic organisms, including insects and mites. Over the past 30 years, considerable effort has been directed at elucidation of the nature of the clock mechanism that underlies photoperiodism. Mathematical models using a number of insect systems have been developed that attempt to causally relate the circadian clock to photoperiodic time measurement. Although some experimental evidence supports these circadian-based models, some insects and mites appear to utilize a non-periodic hourglass timer as the photoperiodic clock. Future work in this field would benefit by following the approach that has proven to be very successful in identifying genes and gene products that regulate circadian rhythmicity in Drosophila melanogaster.

Journal Article↗

Serum house dust mite antibodies: predictor of increased bronchial responsiveness in adults of a community.

The purpose of this study was to determine whether the presence of serum specific immunoglobulin E (IgE) antibodies was associated with increased bronchial responsiveness in adults. We studied cross-sectionally a random community sample of 18-73 year old adults, of whom 83% (n = 489) performed bronchial responsiveness testing as well as serum measurements of five specific IgE antibodies. In the crude data, 39% of those with house dust mite antibodies (n = 18) had a bronchial responsiveness < or = 32 g.L-1 methacholine compared with 19% in subjects without any of the five specific IgE antibodies (n = 453). The corresponding percentages for subjects with timothy antibodies (n = 16) was 25%, birch antibodies (n = 13) 23%, cat antibodies (n = 10) 40% and mould antibodies (n = 2) 50%. When assessing the multivariate relationship between the presence of one specific IgE antibody and degree of bronchial responsiveness we used a semi-proportional hazards model with the response as a 20% fall in forced expiratory volume in one second (FEV1) from pretest value. Covariates included in the model were: gender, age, pretest FEV1, smoking habits, pack-years, season and other specific IgE antibodies than that examined. The presence of house dust mite antibodies was a significant predictor (p < 0.01) of increased bronchial responsiveness in never- and ex-smokers. Indoor allergic sensitization (house dust mite, cat and mould) was a significant predictor of increased bronchial responsiveness, while outdoor allergic sensitization (timothy and birch) was not. Excluding subjects with obstructive lung disease (n = 39) or including the covariate log total serum IgE as a potential confounder yielded the same result. Thus, in this community, indoor allergic sensitization rather than allergic sensitization per se was related to increased bronchial responsiveness after adjusting for other relevant covariates.

Adolescent↗