Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.65 (Der p 1)
 346 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic inflammatory responses are regulated by cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] produced by CD4+ helper (Th0 and Th2) cells. The activation of these T cells follows engagement of T-cell antigen receptors (TCR) by antigenic peptides complexed with major histocompatibility complex (MHC) class II molecules. Under defined conditions presentation of T-cell epitopes as peptides can downregulate immune responses, and here we discuss the potential of peptide-mediated immunotherapy in the regulation of responses to the house dust mite (HDM). Cloning the major allergens of HDM has allowed detailed analysis of the HDM-reactive T-cell repertoire and has revealed that MHC class II restriction is heterogeneous, involving HLA-DP,-DQ, and -DR molecules, and that multiple T-cell epitopes are recognized. There is, however, evidence for a bias in TCR gene usage, which has prompted the analysis of peptide-mediated densitization of human T cells in vitro. CD4+ T cells exposed to high concentrations of HDM peptides become refractory to restimulation and fail to provide B-cell help. This is accompanied by complex changes in the surface phenotype, including the downregulation of TCR and CD28. During the induction of anergy cytokine-specific mRNA levels are enhanced, but when the anergic T cells are restimulated they fail to secrete IL-4 and IL-5, although interferon (IFN)-gamma production may remain unaltered. The ability of peptides to modulate the function of HDM-specific T cells in vivo has been investigated in mice. Following inhalation of peptide containing a major T-cell epitope of Der p 1 (residues 111-139) transient T-cell activation was observed prior to the inhibition of responses in naive and sensitized mice. T cells from the tolerant mice restimulated in vitro produced low levels of cytokines and failed to provide help for B cells.
Clin Immunol Immunopathol 1996 Sep
PMID:From epitopes to peptides to immunotherapy. 881 Oct 60

We investigated the levels of mite allergens (Der p 1, Der f 1, Der 2, and Lep d 1) in dust samples from the homes of 59 patients with asthma, 36 sensitized to house-dust mites (HDM) and 23 to grass pollen (controls), living in Porto, northern Portugal. The relationship between exposure and sensitization to HDM and the influence of housing conditions on mite-allergen levels were also evaluated. Der p 1 (median 9.2 micrograms/g) and Der 2 (4.6 micrograms/g) were the main allergens, while Der f 1 and Lep d 1 levels were always < 1 microgram/g dust and undetectable in 11% and 47% of samples, respectively. All HDM-sensitized asthmatics were exposed to Der p 1 levels > 2 micrograms/g and their homes contained significantly higher levels of Der p 1 (median 12.5 vs 6.4 micrograms/g; P = 0.008) and Der 2 (6.2 vs 3.0 micrograms/g; P = 0.004) when compared to the control group. A significant correlation was observed between the exposure to Der p 1 and the wheal area at skin testing with the Dermatophagoides pteronyssinus (Dp) extract (P = 0.01) as well as with serum specific IgE levels to Dp (P = 0.03). Patients with higher levels of serum specific IgE (> or = 17.5 HRU/ml) were also more frequently exposed to Der p 1 levels > or = 10 micrograms/g (P = 0.002). Old homes, presence of carpets, and signs of dampness were conditions associated with significantly higher levels of mite allergens. In conclusion, we found high levels of Der p 1 and Der 2 particularly in the homes of HDM-sensitized patients and we confirm the relationship between exposure and sensitization to HDM, assessed by both in vivo and in vitro methods. In additional to a favorable outdoor climate, we found in our region housing conditions propitious to mite growth, suggesting that specific geographic characteristics must also be taken into account for the correct planning of mite-avoidance measures.
Allergy 1996 Sep
PMID:Indoor mite allergens in patients with respiratory allergy living in Porto, Portugal. 889 15

DNA immunization has been an attractive approach in altering the host immune response to antigen. To examine the utility of DNA immunization in allergic response, we examined the in vivo efficacy of an 'allergen-gene immunization' approach in the modulation of allergen-specific IgE responses in mice. Our results showed first that I.m. injection of a gene construct (pCMVD) containing an important house dust mite allergen gene (Dermatophagoides pteronyssinus group 5 allergen; Der p 5) results in the induction of Der p 5-specific IgG antibodies, but not IgE antibody. We next examined the effect of transduced allergen gene on the expression of specific IgE response in mice after i.p. challenge with recombinant Der p 5 (rDer p 5). Both vector (mock) control- and pCMVD-treated mice were i.p. sensitized with rDer p 5 at 3 weeks after injection of gene construct. Results showed that there is a 90% reduction in the level of specific IgE in pCMVD-treated mice when compared with mock-treated mice. Furthermore, the suppression of specific IgE response can be adoptively transferred with CD8+ T cells from pCMVD-treated mice and such inhibition is in an antigen-specific manner, since the level of specific IgE to an irrelevant allergen, Der p 1, remained unchanged in comparison to that of the mock-treated group. In addition, Der p 5-specific CD8+ T cells could produce high levels of IFN-gamma which probably inhibit allergen-specific IgE responses. Taken together, our results suggest that allergen-gene transfer is effective in the modulation of allergen-specific IgE responses and may provide a novel therapeutic approach.
Int Immunol 1996 Sep
PMID:Inhibition of specific IgE response in vivo by allergen-gene transfer. 892 18

This double-blind, placebo-controlled study investigated whether the application of an acaricide (Acarosan) on mattresses and on textile floor coverings in living rooms and bedrooms can contribute to improvement in lung function and airway hyperresponsiveness in 40 adult asthmatic patients sensitized to house-dust mite. In a second group of 19 patients who refused chemical intervention, the clinical effects of application of allergen-impermeable mattress encasings were studied. In all three treatment groups, Der p 1 levels in mattress dust were statistically significantly decreased after 12 months. However, this decrease was much greater in the group who received mattress encasings (final mean level 430 ng/g) than in groups with acaricide- or placebo-treated mattresses (final mean levels 1730 and 2100 ng/g, respectively). Treatment of textile floors with either Acarosan or placebo chemical caused a statistically significant decrease in the level of the house-dust-mite allergen Der p1 in floor dust. In the group with mattress encasings, no significant changes of floor dust Der p 1 were found. Airway hyperresponsiveness (as measured by the PC20 histamine) improved significantly in the mattress cover group after 6 months. The Acarosan group also showed a small but statistically significant improvement after 12 months.
Allergy 1997 Sep
PMID:Allergen-avoidance measures in homes of house-dust-mite-allergic asthmatic patients: effects of acaricides and mattress encasings. 929 77

The avoidance of house dust mite allergens is a major area of interest and essentially requires a significant removal of these allergens from the immediately respirable air. Electrostatic attraction and anchoring of particulate matter using electret polymers is commonly used for air filtration purposes. This effect is investigated for its possible use in domestic allergen avoidance. Polypropylene electret, heat-treated electret and non-electret, and wool and nylon fibre samples were soiled with house dust known to contain Der p 1 allergen. These samples were vacuumed at three air face velocities. The proportions of released and anchored dust were calculated. Released dust was collected and analysed for Der p 1 concentration and compared to stock dust values. Results showed that compared to uncharged fibres at least 95% more dust remained anchored in the electret fibres. Also, overall Der p 1 release was reduced by more than 49%. Der p 1 allergen concentrations in the collected dust were relatively constant for all the fibres tested, indicating no selective attraction or repulsion of Der p 1 allergen carrying particles in the experimental dust. The consistently high dust anchoring ability of the electret fibres could be used in many domestic products that are known to harbour particulate allergens, to reduce their release and inhalation.
Med Biol Eng Comput 1998 Sep
PMID:Dust anchoring characteristics of electret fibres with respect to Der p 1 allergen carrying particles. 1036 47

The effect of two allergen avoidance modalities, Allergy Control Covers (ACC) and High Efficiency Particulate Filters (HEPA) on asthma control in children were evaluated. This was an open study involving 24 dust mite sensitive asthmatic children. Following a 4 week run-in period, the subjects were randomly allocated to use mattresses fitted with ACC (n = 6), HEPA filters in their bedrooms (n = 12) or act as controls (n = 6) for a study duration of 4 months. Measurements of the major Dermatophagoides spp. mite allergens, Der p 1 and Der f 1, levels in dust samples obtained from mattresses were made at baseline, 1, 2 and 4 months post implementation. Daily symptom scores including morning and evening peak flow readings, and monthly spirometry and exercise bronchoprovocation tests were carried out Our results showed that dust mite allergen levels in mattresses fell at 1 and 2 months post implementation in the ACC group (p<0.05). In contrast, no decrease in allergen levels was seen in the HEPA and control group. At the end of the 16 weeks, only the ACC group showed improvement in FEV1 and reduction in diurnal peak expiratory flow rate (p<0.05). Improvement in mean symptom scores was also observed for both the ACC and HEPA groups, but not the control groups (p<0.05). Although the numbers in this study were small, the results Indicate that the effectiveness on mite exposure barrier covers was short-lived, and the improvement in asthma control though documented was not obvious.
Asian Pac J Allergy Immunol 1999 Sep
PMID:An evaluation of mattress encasings and high efficiency particulate filters on asthma control in the tropics. 1069 55

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.
Asian Pac J Allergy Immunol 1999 Sep
PMID:Sensitization to Blomia tropicalis and dermatophagoides pteronyssinus-a comparative study between Singapore and Taiwan. 1069 57

The authors investigated the relationship between respiratory symptoms in adults and exposure to mite and cat allergens, the role of endotoxins in house dust, the effects of mixtures of several allergens, and interactions between allergen exposure and allergic sensitization. Within a nested case-control study, 405 subjects aged 25-50 yrs from two German cities answered a standardized questionnaire. Allergen-specific immunoglobulin-E was measured. Dust samples were taken from the subjects' homes to determine exposure to mite (Dermatophagoides pteronyssinus antigen 1 Der p 1) and (D. farinae antigen 1 Der f l) and cat (cat antigen d1 Fel d 1) allergen and endotoxin content in settled house dust. Exposure to Der f 1 and Der p 1 plus Der f 1 >10 microg x g(-1) of mattress dust, respectively, increased the risk of wheeze and breathlessness (odds ratios (OR): 4.04, 95% confidence interval (CI): 1.53-10.64, OR: 2.78, 95% CI: 1.06-7.28). Fel d 1 >8 microg x g(-1) was positively associated with cough at night (OR: 2.74, 95%, CI: 1.22-.17), noteworthy also in the nonsensitized subjects. Subjects exposed to elevated concentrations of more than one allergen had an up to seven-fold increase in the risk of respiratory symptoms, compared to nonexposed subjects. Sensitized subjects exposed to elevated concentrations of Der f 1 or Fel d 1 were found to have the highest risk of asthma attacks and respiratory symptoms. No statistically significant association was found between exposure to endotoxins and respiratory health. Indoor exposure to Dermatophagoides farinae antigen 1 and cat antigen d1 is a risk factor for respiratory symptoms in adults, and for cat antigen d 1 even in nonsensitized subjects. The risk is increased if subjects are exposed to a mixture of allergens or if they are sensitized in addition to high exposure.
Eur Respir J 2001 Sep
PMID:Respiratory symptoms in relation to indoor exposure to mite and cat allergens and endotoxins. Indoor Factors and Genetics in Asthma (INGA) Study Group. 1158 55

House dust mites (HDM) are the most common source of aeroallergens and in genetic susceptible individuals can cause symptoms ranging from atopic dermatitis to bronchial asthma. Der p 1, a major target of the human immune responses to HDM, through its enzymatic properties can modulate the adaptive immune system by the cleavage of CD23 and CD25. The consequences of this would be to promote allergic inflammatory responses. Furthermore, by disrupting epithelial tight junctions Der p 1 facilitates the transport of allergen across the epithelium. Here, we report that Der p 1 has additional effects on the innate defense mechanisms of the lung, by inactivating in vitro and ex vivo the elastase inhibitors human (h) alpha1-proteinase inhibitor (h-A1-Pi), mouse (m-), (but not human [h])-SLPI and h-elafin. We confirm that Der p 1 contain both cysteine and serine proteinases, and extend this finding to demonstrate for the first time that h-elafin is particularly sensitive to the biological activity of the latter. Because these elastase inhibitors have antimicrobial, as well as antielastase activity, our results suggest that inactivation of these innate components of the lung defense system by Der p 1 may increase the susceptibility of patients with allergic inflammation to infection.
Am J Respir Cell Mol Biol 2003 Sep
PMID:House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors. 1268 23

Exposure to allergens from house dust-mites (Der p 1) and domestic cats (Fel d 1) is associated with symptom severity in atopic subjects with asthma and rhinitis. Assessment of allergen exposure in the domestic environment is normally determined by measurement from a single floor site. We determined the variability of these allergens and protein throughout the whole living room floor area. Dust samples were collected from 1 m2 areas from 16 carpeted living room floors in Wellington, New Zealand, and analyzed for concentrations of Der p 1 and Fel d 1. Mean coefficients of variation for Der p 1 and Fel d 1 were 53.1% (range: 28.5-136.8) and 65.6% (range: 28.5-131), respectively. This study has demonstrated a large variation of house dust-mite and cat allergens within living room floors and thus a single sampling site may not be representative for assessment of an individual's exposure risk. House dust-mite and cat allergen levels from the center of the room, in front of a couch or chair, or from a corner of the room are similar to mean levels from the whole room, these sites may thus be representative of the whole living room floor in large-scale epidemiological studies.
Indoor Air 2003 Sep
PMID:House dust-mite allergen and cat allergen variability within carpeted living room floors in domestic dwellings. 1471 24


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