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PubMed2004

Microbial characterization of free floating condensate aboard the Mir space station.

Three samples of humidity condensate that had accumulated behind panels aboard the Russian space station Mir were collected and returned to earth for analysis. As these floating masses of liquid come into contact with the astronauts and the engineering systems, they have the potential to affect both crew health and systems performance. Using a combination of culturing techniques, a wide variety of organisms were isolated included Escherichia coli, Serratia marcescens, and a presumed Legionella species. In addition, microscopic analysis indicated the presence of protozoa, dust mites, and spirochetes. These findings suggest the need for more comprehensive microbial analysis of the environment through the use of new methodologies to allow a more thorough risk assessment of spacecraft.

Animals↗
PubMed2003

Mechanisms of tolerance to inhalant allergens: the relevance of a modified Th2 response to allergens from domestic animals.

Subjects can be "non-allergic" because (1) they are not exposed, (2) they fail to make an immune response, or (3) they make an immune response that does not include IgE antibodies (Ab). The recent observation that children raised in a house with a cat are less likely to become allergic to cat allergen than those who only get indirect exposure provides a model to investigate the factors controlling allergic responses. Many of these highly exposed children have made an IgG and IgG4 Ab response to Fel d 1 without IgE Ab, i.e., a "modified Th2 response". In countries where cats are a major cause of asthma, the presence of a cat may decrease the risk of asthma. By contrast, in countries with high exposure to dust mites, cats can induce specific tolerance to Fel d 1 without influencing asthma or the IgE Ab response to dust mites. Using overlapping peptides to investigate T cell responses to Fel d 1 suggests that the structure of the molecule plays a special role in inducing the T cell responses that can "control" the immune response to cat allergens. This T cell response is characterized by high levels of IL-10 production, but this is not restricted to those who have made a modified Th2 response. The results suggest that there are major differences in the immune response to different allergens that profoundly affect their role in allergic disease. Dust mite and cockroach differ from cat (and rat) allergens not only in the quantity inhaled and the particles' sizes but also in the biochemistry of the molecule.

Allergens↗
PubMed2006

Occupational sensitization to storage mites in the personnel of a water-damaged grocery store.

OBJECTIVES: To investigate the occupational exposure and sensitization to storage mites (SM) in sales staff working in a moisture-damaged and three healthy reference buildings. METHODS: The study population consisted of the entire personnel (n=12) in the moisture-damaged grocery store. They all suffered from persistent upper respiratory tract symptoms. Twelve (in results 11) symptom-free controls working in three healthy reference groceries were matched with age, sex and occupation. Dust samples from each building were examined for mites. The clinical study consisted of otorhinolaryngological examination and determination of IgE reactivity. Specific serum IgE antibodies were measured against three SMs and two house dust mites (HDM). Skin prick tests (SPT) were made to the same five mites and to five common aeroallergens. If sensitization to any of the SMs was detected, a nasal provocation test (NPT) was performed. RESULTS: SMs were found in all buildings. In all, seven cases and four control subjects showed IgE-mediated reactivity. Sensitization to mites was detected in six cases and in three controls and in 2/12 and 3/11 this was the only IgE antibody response observed. In addition, one case and one control subject were sensitized to common aeroallergens. NPT with SMs was positive in four cases and in one control. CONCLUSIONS: In grocery stores, the personnel are exposed to SMs. The risk of sensitization to mites is obvious and an IgE response can occur without any reactivity to common aeroallergens. SM allergy may in some cases explain the chronic rhinitis related to moisture-damaged buildings.

Animals↗
PubMed2004

Penetration of light into carpet, and responses of the European house-dust mite (Dermatophagoides pteronyssinus) to varying light intensity and diurnal cycle.

This study examined the question of what effect exposure to light might play in determining the vertical distribution of house-dust mites in carpet, and the degree to which light penetrates worn and unworn carpets of different pile conformation (loop- versus cut-pile), height and colour. The effect on population increase of a diurnal lighting cycle versus continual darkness was also investigated. It was found that the penetration of light into carpets was largely unaffected by pile colour or conformation. Pile height was an important factor, however, and for a given height within the pile, light intensity was higher in carpets subjected to a greater degree of wear. This corresponded to the reduction in effective pile height that occurs with carpet use. Whilst the differences observed were sometimes large (up to two-fold for a given height within the pile), Petri dish studies suggested no mite preference for habitation of areas of low light intensity compared to high intensity. Additionally, culturing mites under a diurnal light cycle was shown to be no more efficient than culturing in complete darkness. These results suggest that exposure to light is not an important determinant of house-dust mite behaviour, or their ability to colonise textile substrates.

Animals↗
PubMed2006

Mite immunotherapy.

Dermatophagoides pteronyssinus and D. farinae are the most common house dust mites and are among the most common sources of indoor allergens worldwide. These species are very common in humid regions, where most allergic individuals are sensitized to house dust mites. Specific immunotherapy with mite extracts has demonstrated clinical benefits in several double-blind, placebo-controlled trials that are included in recent reviews of subcutaneous immunotherapy, including pediatric and adult patients with rhinoconjunctivitis and or asthma. Most successful studies of mite immunotherapy have used native allergen extracts adsorbed onto aluminum hydroxide, or chemically modified mite-allergen extracts. Several studies have also shown efficacy using sublingual immunotherapy in pediatric and adult patients with asthma and/or rhinitis. Additionally, the efficacy of subcutaneous immunotherapy has been demonstrated in patients with atopic dermatitis, although more double-blind, placebo-controlled studies are needed. Based on several studies, it cannot be concluded that mite immunotherapy is more dangerous or safer than immunotherapy with grasses, epithelia, or animal epithelia. Because the delivery of high doses of allergen carries with it the risk for immunoglobulin E (IgE)-mediated events, several methods have been developed to reduce specific IgE binding to mite-allergen extracts. An important challenge for future mite immunotherapy modalities is the delivery of relatively high doses without a significant risk for severe reactions.

Allergens↗
PubMed2004

High-level expression of a codon optimized recombinant dust mite allergen, Blo t 5, in Chinese hamster ovary cells.

Blo t 5 is a major allergen from house dust mite Blomia tropicalis. Purification of native Blo t 5 (nBlo t 5) from whole dust mite extract is tedious and gave low yield. In this study, we demonstrated that codon optimization facilitated high-level expression of Blo t 5 in Chinese hamster ovary (CHO)-K1 cells and thus allows production of sufficient recombinant cBlo t 5 for specific immunotherapy. A codon optimized Blo t 5 gene was synthesized by PCR and the codon optimized or wild-type Blo t 5 gene in pcDNA3.0 was transfected into CHO-K1 cells and stably selected with Geneticin (G418). Western-immunoblot analysis of spent culture media detected a positive band at 14kDa for the codon optimized but not wild-type gene transfectants. In addition, a stable CHO-K1 clone produced up to 13 mg/L of the cBlo t 5 protein having a high correlation of human IgE reactivities and allergenicity to the native Blo t 5, thus indicating proper conformation of this recombinant form.

Allergens↗
PubMed2005

Recombinant Der p 1 and Der f 1 exhibit cysteine protease activity but no serine protease activity.

Although mite major group 1 allergens, Der p 1 and Der f 1, were first isolated as cysteine proteases, some studies reported that natural Der p 1 exhibits mixed cysteine and serine protease activity. Clarifying whether the serine protease activity originates from Der p 1 or is due to contamination is important for distinguishing between the pathogenic proteolytic activities of group 1 allergens and mite-derived serine proteases. Recombinant mite group 1 allergens would be useful tool for addressing this issue, because they are completely free from contamination by mite serine proteases. Recombinant Der p 1 and Der f 1, and highly purified natural forms exhibited only cysteine protease activity. However, commercially available natural forms exhibited both activities, but the two activities were eluted into different fractions in size-exclusion column chromatography. The substrate specificity associated with the serine protease activity was similar to that of Der f 3. These results indicate that the serine protease activity does not originate from group 1 allergens.

Antigens, Dermatophagoides↗
PubMed2005

Crystal structure and some properties of a major house dust mite allergen, Derf 2.

Pyroglyphid house dust mites are a major source of allergens in house dust. Mite allergens sensitize and induce asthma, rhinitis, and eczema in a large portion of patients with allergic diseases. Here, the crystal structure of a major mite allergen, Derf 2, derived from Dermatophagoides farinae was solved by single isomorphous replacement method with anomalous scattering (SIRAS) at 2.1A resolution. The present study also demonstrated that the conformation of the allergen was critical in the determination of Th1/Th2 shift based on physicochemical and immunological analyses. This indicates that rigidly folded and singly dispersed structure is essentially required for the generation of Th2 type cells by the allergen, while conformational variant protein leads to Th1 skewing, irrespective of the same amino acid sequence. This structure/function relationship may allow us to develop a novel strategy for hyposensitization therapy in patients with allergic diseases triggered by house dust mite allergens.

Animals↗
PubMed2025

Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages.

M2 macrophages (M2 cells) are known to be involved in both Th2 responses and immune regulation. However, the underlying mechanisms remain unclear. Functional abnormalities in macrophages are associated with airway allergy (AA). The objective of this study was to investigate the role of methyltransferase-like 5 (Mettl5) in macrophages and its potential to alleviate AA. In this study, an airway allergy (AA) mouse model was established using dust mite extracts (DME) as the specific antigen. M2 cells were collected from mice with and without AA. The role of Mettl5 in modulating the immune activities of M2 cells was assessed using both epigenetic and immunological approaches. We found that Mettl5 levels were elevated in airway M2 cells from mice with AA. The presence of Mettl5 in airway M2 cells was positively correlated with airway Th2 polarization in these mice. Airway M2 cells from AA mice exhibited impaired immune-suppressive function, which was resolved by ablating the Mettl5 gene in macrophages. Mettl5 was responsible for the hypermethylation of the Il10 promoter in airway M2 cells of AA mice. Exposure to DME induced Mettl5, which in turn recruited USP21 to deubiquitinate GATA3, thereby boosting IL-4 expression in M2 cells. Inhibiting Mettl5 restored the immune-suppressive capacity of airway M2 cells and mitigated experimental AA. In conclusion, Mettl5 plays a critical role in subverting the immune-regulatory capacity and enhancing IL-4 expression in M2 cells. Inhibition of Mettl5 can mitigate experimental AA by restoring the immune-regulatory functions of M2 cells.

Animals↗
PubMed2005

The relationship between persistent organic pollutants in maternal and neonatal tissues and immune responses to allergens: A novel exploratory study.

BACKGROUND: Modern persistent organic pollutants (POPs) contamination are logical candidates in the investigation of the, as yet, unexplained association between allergic disease and progressive industrialisation. POPs have been detected in human cord blood, placental tissues and breast milk, and the reported association between cord blood IgE levels and cord/placental POP levels has raised concerns about potential immunological effects in early life. METHODS: The initial aim of this study was to determine if POPs were detectable in maternal blood, cord blood, placental tissues, adipose tissue and breast milk samples from randomly selected Western Australian women (n = 31), where allergic disease is epidemic. Gas chromatography was used to detect polychlorinated biphenyl compounds [PCBs] (as Aroclor 1232, 1254, 1260) and organochlorine (OC) pesticides, including p,p'-DDT, p,p'-DDE, hexachlorobenzene (HCB), lindane, heptachlor epoxide, dieldrin and chlordane. Secondly, we assessed the relationship between POP levels detected in vivo and maternal and neonatal responses (cytokine and lymphoproliferation) to allergens and mitogens. RESULTS: Low level POP contamination was detected in adipose tissue and breast milk (but not in cord blood, maternal blood or placental tissues). The most ubiquitous compound found in over 90% of adipose tissues samples was a OC metabolite of DDT, p,p'-DDE (median 0.07 mg/kg; interquartile range [IQR] 0.05-0.12). However, the majority of other OC compounds were not detectable and PCB were not detectable in any samples. The three main residues detected in breast milk were p,p'-DDE (0.003 mg/l; 0.001-0.009), dieldrin (0.001 mg/l; 0.001-0.046) and HCB (0.001 mg/l; 0.001-0.001). These levels are significantly lower than reported over 20 years ago. There were no consistent relationships between POP levels in vivo and maternal or infant responses, with the exception of a significant inverse association (Spearman rank correlation: r = -0.406, p = 0.049) between maternal adipose tissue levels of OC p,p'-DDE and maternal T helper cell Type 1 interferon [IFN] gamma to mitogens. CONCLUSION: This study provides the first evidence (in Australia) since the early 1990's that adipose OC levels have continued to fall. The negligible levels in this randomly selected group are significantly lower than those previously recorded, suggesting that POP contamination (at biologically relevant levels) is not likely to be a major contributing factor in the increasing rates of allergy in Western Australia. However, the relationship between Th1 immune function and OC contamination is consistent with other reports and is worth investigating as a relevant factor in populations where OC contamination is greater.

Adipose Tissue↗
PubMed2005

Effects of allergen inhalation and oral glucocorticoid on concentrations of serum-soluble CD86 in allergic asthmatics.

The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum soluble CD86 in patients with allergic asthma. Our results showed that the serum soluble CD86 concentrations in the dual responder group increased from 491.8 +/- 15.4 IU/ml before allergen inhalation to 603.8 +/- 19.3 IU/ml 24 h after allergen inhalation. In the isolated early responders, there was no significant increase in serum soluble CD86 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum soluble CD86 concentrations after 2 weeks of glucocorticoid therapy (448.3 +/- 15.1 IU/ml) compared with baseline values (532.7 +/- 12.3 IU/ml), whereas there was no significant difference in the placebo group. This study has demonstrated that serum soluble CD86 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCD86 concentrations were downregulated by prednisolone therapy.

Administration, Inhalation↗
PubMed2006

Adenosine A1 receptor antagonist versus montelukast on airway reactivity and inflammation.

Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating adenosine A(1) receptors. Previously, it is reported that a high dose of L-97-1, a water-soluble, small molecule adenosine A(1) receptor antagonist, blocks early and late allergic responses, and bronchial hyper-responsiveness to histamine in a hyper-responsive rabbit model of allergic asthma. Effects of a lower dose of L-97-1 are compared to montelukast, a cysteinyl leukotriene-1 receptor antagonist on early allergic response, late allergic response, bronchial hyper-responsiveness, and inflammatory cells in bronchoalveolar lavage (BAL) fluid following house dust mite administration. Rabbits received intraperitoneal injections of house dust mite extract within 24 h of birth followed by booster house dust mite injections. Hyper-responsive rabbits received aerosolized house dust mite (2500 allergen units), 1 h after intragastric administration of L-97-1 (1 mg/kg) or montelukast (0.15 mg/kg) and lung dynamic compliance was measured for 6 h. Lung dynamic compliance was significantly higher following L-97-1 at all time points and with montelukast at 60-300 min following house dust mite (P<0.05). L-97-1 blocks both early and late allergic responses. Montelukast blocks only the late allergic response. Both L-97-1 and montelukast significantly blocked bronchial hyper-responsiveness at 24 h (P<0.05). Both L-97-1 and montelukast significantly reduced BAL eosinophils at 6 h and neutrophils at 6 and 24 h (P<0.05). L-97-1 significantly reduced BAL lymphocytes at 6 and 24 h (P<0.05). Montelukast significantly reduced BAL macrophages at 6 and 24 h (P<0.05). By blocking both bronchoconstriction and airway inflammation, L-97-1 may be an effective oral anti-asthma treatment.

Acetates↗
PubMed2005

Structure of the house dust mite allergen Der f 2: implications for function and molecular basis of IgE cross-reactivity.

The X-ray structure of the group 2 major allergen from Dermatophagoides farinae (Der f 2) was determined to 1.83 A resolution. The overall Der f 2 structure comprises a single domain of immunoglobulin fold with two anti-parallel beta-sheets. A large hydrophobic cavity is formed in the interior of Der f 2. Structural comparisons to distantly related proteins suggest a role in lipid binding. Immunoglobulin E (IgE) cross-reactivity between group 2 house dust mite major allergens can be explained by conserved surface areas representing IgE binding epitopes.

Allergens↗
PubMed2004

High IFN-gamma production by CD8+ T cells and early sensitization among infants at high risk of atopy.

BACKGROUND: High genetic risk (HR) of atopy among unstratified populations of infants is associated with attenuated IFN-gamma responses. However, the role of IFN-gamma in progression from HR status to active disease is less clear. OBJECTIVE: To identify immune function markers in neonates with HR that are associated with positive atopic outcomes at 2 years. METHODS: Cord blood mononuclear cells (CBMCs) were collected from 175 children with HR and cryopreserved. The children were assessed for atopy by skin prick at 0.5 and 2 years. CBMCs were thawed and stimulated with allergens and mitogens PHA and staphylococcal enterotoxin B (SEB), and cytokine responses were determined. RESULTS: No correlations were observed between allergen-specific CBMC responses and atopic outcomes. In contrast, sensitization was strongly associated with polyclonal IFN-gamma responses to both PHA (P=.002) and SEB (P=.005), and also with SEB-induced IL-5 (P =.05), IL-10 (P =.02), and IL-13 (P =.01). Logistic regression analysis identified elevated PHA-induced IFN-gamma and SEB-induced IL-13 responses as the strongest independent predictors of atopy development. Cell separation studies confirmed CD8+ T cells as the source of approximately 90% of IFN-gamma production. CONCLUSIONS: IFN-gamma produced by CD8+ T cells may synergize with T(H)2 cytokines in driving atopy development in children with HR.

Allergens↗
PubMed2004

Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite.

BACKGROUND: Although several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown. OBJECTIVE: A double-blind, placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite (HDM; Dermatophagoides species) was conducted to assess the effects of specific immunotherapy added to guideline-adjusted pharmacologic treatment and allergen avoidance. METHODS: After 1 observational year of pharmacologic treatment and standard measures of HDM avoidance, 2 groups of asthmatic subjects were randomly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine (n=41) or placebo (n=31) for 3 years. Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines. RESULTS: The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects. The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators, an increase in morning and evening peak expiratory flow, and a reduced skin sensitivity to HDM extracts. The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids, asthma symptoms, lung volumes, or bronchial responsiveness to methacholine. CONCLUSION: These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits, possibly by reducing the allergic response of asthmatic patients sensitized to HDM.

Administration, Inhalation↗
PubMed2004

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.

Antigens, Dermatophagoides↗
PubMed2004

Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study.

BACKGROUND: Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known. OBJECTIVE: To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma. METHODS: A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization. RESULTS: There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1% (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05; number needed to treat, 14). No significant differences in wheeze were found with either intervention. CONCLUSION: These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.

Adult↗