Environmental control in childhood asthma.
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Allergens↗
Biomedical subjects
M D Chapman
Publications and source records attributed to M D Chapman.
IgE antibodies to recombinant forms of Fel d I: dichotomy between fluid-phase and solid-phase binding studies.
BACKGROUND: The major cat allergen Fel d I consists of two polypeptide chains linked by disulfide bonds, each of which has been expressed in bacteria. To investigate the antigenic structure of Fel d I, antibody binding to the native molecule and to each recombinant chain were compared. METHODS: Polyclonal human IgE and IgG antibodies and monoclonal antibodies (mAbs) to Fel d I were compared for binding to Fel d I, chain 1, or chain 2 by fluid-phase inhibition radioimmunoassay, RAST, and immunoabsorption. RESULTS: In the fluid-phase assay, neither recombinant chain significantly inhibited the binding of antibody to native Fel d I at concentrations of up to 10 micrograms/ml. Partial inhibition was observed when chain 1 was used, which inhibited the binding of two mAbs by 40% and 75%. In contrast, when the solid-phase RAST assay was used, IgE antibodies bound both chains with high specificity, and there was a good quantitative correlation between IgE antibody binding to Fel d I and both chain 1 (r = 0.58, p < 0.01) and chain 2 (r = 0.47, p < 0.01). Up to 70% of IgG or IgE anti-Fel d I antibodies could be absorbed by either chain 1 or chain 2, and both chains in combination produced similar absorption values in response to native Fel d I. Four mAbs were fully absorbed by chain 1, but not chain 2, and three mAbs were not absorbed by either chain. CONCLUSIONS: The results demonstrate a dichotomy between antibody binding to recombinant Fel d I chains, which may be explained by confirmational differences between the chains in the fluid phase or on solid supports. The results also suggest that chain 1 is an important site for mAb-defined B-cell epitopes on Fel d I.
Glycoproteins↗
Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens: relation to sensitization and asthma among children living in Los Alamos, New Mexico.
BACKGROUND: Our objective was to identify the allergens associated with asthma among schoolchildren in an area of the United States where dust mite growth is expected to be poor. Los Alamos, N.M., was chosen because it has low rainfall and is at high altitude (7200 feet) making it very dry. One hundred eleven children (12 to 14 years old) from the middle school who had been previously classified according to bronchial hyperreactivity to histamine (BHR) were studied. METHODS: Sera were assayed for IgE antibodies to mite, cat, dog, cockroach, Russian thistle, and grass pollen, with both CAP system fluoroimmunoassay (Kabi Pharmacia, Uppsala, Sweden) and conventional RAST. Allergens were measured in dust samples from 108 homes with two-site assays for mite (Der p 1 and Der f 1), cat (Fel d 1), dog (Can f 1), and cockroach (Bla g 2). RESULTS: Concentrations of dog and cat allergens were elevated in almost all houses with pets but were also high in a significant proportion of the houses without pets. Levels of mite allergen were less than 2 micrograms/gm in 95% of the houses, and cockroach was undetectable in all but two of the houses. Among the 21 with BHR who had symptoms, 67% had IgE antibody to dog and 62% had IgE antibody to cat. For these allergens IgE antibody was strongly associated with asthma (p < 0.001). By contrast, the presence of IgE antibody to mite, cockroach, or grass pollen was not significantly associated with asthma. CONCLUSION: The high prevalence of IgE antibody to cat and dog allergens among these children is in keeping with the presence of cat and/or dog allergen in most of the houses. Furthermore, sensitization (as judged by IgE antibodies) to cat and dog allergens was strongly associated with asthma. On the other hand, no clear relationship was found between sensitization or symptoms and the current level of allergen in individual houses. The results show that in this mite-and cockroach-free environment sensitization to domestic animals was the most significant association with asthma.
Adolescent↗
The role of indoor allergens in asthma.
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Air Pollution, Indoor↗
Monitoring allergen exposure in asthma: new treatment strategies.
The development of monoclonal antibody-based enzyme-linked immunosorbent assay technology for measuring environmental allergen exposure has provided a benchmark for assessing the role of indoor allergens in causing asthma and other allergic diseases. Epidemiological studies from several parts of the world have shown that immunoglobulin E (IgE)-mediated sensitization to indoor allergens (mite, cat, dog and cockroach) is a risk factor for asthma attacks. A dose-response relationship between allergen exposure and sensitization has been demonstrated for mite allergens, and threshold values for exposure levels leading to sensitization or to exacerbations of symptoms have been defined. Comparative studies on airborne allergen levels have made it possible to determine the properties of aeroallergen particles, their concentration in indoor air, and the relationship to clinical symptoms. Together, these studies provide strong evidence that allergen exposure plays a causal role in the development of bronchial hyperreactivity and of the chronic inflammatory responses seen in patients with asthma. Logically, the primary preventive treatment should be allergen avoidance. Through knowledge of indoor allergen levels, both in dust and in the air, different avoidance strategies have been applied to the various indoor allergens, and there is increasing evidence of their clinical efficacy. Monitoring allergen levels in patients' houses should improve their understanding of the role of allergens in asthma and improve compliance with avoidance measures.
Allergens↗
Immunochemical and molecular methods for defining and measuring indoor allergens: in dust and air.
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Air Pollution, Indoor↗
Chemical treatment of carpets to reduce allergen: a detailed study of the effects of tannic acid on indoor allergens.
Tannic acid (TA), a protein-denaturing agent, has been reported to reduce allergen levels in house dust and is marketed for that purpose as 1% and 3% solutions. We investigated the effects of TA on dust allergens by using monoclonal antibody-based ELISAs for mite (Der p I, Der f I, and group II) and cat (Fel d I) allergens. Initial studies confirmed that TA reduced allergen levels in carpet dust. However, when dust samples from treated carpets are extracted in saline solution, residual TA redissolves and may interfere with the assessment of allergens. In the laboratory, concentrations of TA as low as 0.1% inhibited the assays, but this effect may be prevented by addition of 5% bovine serum albumin (BSA). After treatment of dust samples in the laboratory with 3% TA, the apparent reductions in Der p I and Der f I levels were 89% and 96%, respectively, but when the samples were extracted in 5% BSA the reductions were 74% and 92%. Similar effects were seen with dust samples from carpets treated with TA. In an extreme case in which a carpet had been repeatedly treated with TA, the apparent concentration of Der p I was < 0.05 microgram/gm without BSA and 2.1 and 8.4 microgram/gm when extracted in the presence of 1% and 5% BSA, respectively. Our testing of the ability of TA to denature Fel d I demonstrated an 80% reduction in allergen, but only in samples with an initial concentration of less than 200 micrograms Fel d I/gm dust.(ABSTRACT TRUNCATED AT 250 WORDS)
Air Pollution, Indoor↗
Monoclonal antibodies to group II Dermatophagoides spp. allergens: murine immune response, epitope analysis, and development of a two-site ELISA.
BACKGROUND: Group II allergens are a major cause of sensitization in patients allergic to mites. To facilitate the antigenic analysis of group II allergens and to develop improved methods of allergen detection, we compared IgG anti-group II antibody responses in inbred mouse strains and raised a panel of monoclonal antibodies (mAbs). METHODS: IgE antibody responses were compared by antigen-binding radioimmunoassay. Epitope specificity of the mAbs was analyzed by two-site binding assays and by cross-inhibition radioimmunoassays. RESULTS: Comparison of polyclonal IgG antibody responses in five BALB congenic strains showed that H-2d mice had poor responses, whereas H-2b and H-2k mice had strong, cross-reactive, IgG anti-group II responses. The specificities of nine anti-Der p II IgE mAbs raised in A/J mice were compared with specificities of seven mAbs produced previously. Most mAbs (11 of 16) recognized common epitopes on Der p II and Der f II: three were specific to Der p II, and two showed high binding to Der f II. Epitope analysis showed that the mAbs defined four cross-reactive, nonoverlapping sites on the group II allergens. Binding of several combinations of mAbs was compared, and a two-site ELISA for group II antigens was developed. Linear regression analysis showed an excellent correlation between results of this assay and group II radioimmunoassay of house dust samples (n = 40, r = 0.85, p < 0.001). CONCLUSIONS: There are multiple cross-reactive B-cell epitopes on group II allergens. The group II ELISA has several important applications, including assessment of environmental allergen exposure, monitoring of the efficacy of avoidance procedures, and standardization of commercial mite allergen extracts.
Allergens↗
Fine specificity of B-cell epitopes on Felis domesticus allergen I (Fel d I): effect of reduction and alkylation or deglycosylation on Fel d I structure and antibody binding.
The repertoire of B-cell epitopes on the major cat allergen, Fel d I, was analyzed with monoclonal antibodies (MoAbs) in topographic mapping studies and in immunoassays with antigen derived from other cat (Felidae) species. Four essentially nonoverlapping epitopes on Fel d I, designated Fd1A to D, were defined by use of 15 anti Fel d I MoAbs in cross-inhibition radioimmunoassay. Only MoAbs directed against epitope Fd1B bound to putative Fel d I homologues in hair and dander extracts from seven other feline species (Panthera species, [n = 5], Leptailurus serval, and Leopardus pardalus). Quantitative monosaccharide analysis showed that Fel d I was a glycoprotein, containing high levels of fucose, as well as glucosamine, galactose, and mannose. Binding of MoAbs and human IgG or IgE antibody to native, reduced and alkylated or deglycosylated Fel d I was compared by means of immunoprecipitation and immunoassay, and the effects of these treatments on the structure of Fel d I were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. On reduction and alkylation, Fel d I dissociated into 14 kd and 3.2 kd peptides, and deglycosylation with trifluoromethane sulfonic acid produced a 12 to 14 kd peptide. These procedures resulted in a 100- to 1000-fold loss in murine or human antibody binding activity and caused significant loss of secondary structure, as judged by circular dichroism spectroscopy. Treatment with potassium hydroxide also caused a marked loss in antigenic reactivity. In contrast, enzymatic deglycosylation generated a 9 kd peptide, which showed strong reactivity with murine and human antibodies, comparable to native Fel d I. The results show that MoAbs define a broad repertoire of B-cell epitopes on Fel d I, one of which is expressed by other cat species. These epitopes are conformational and do not appear to involve oligosaccharide residues.
Alkylation↗
Comparative detection of mite allergens in house dust of homes in Moscow by enzyme-linked immunosorbent assay and acarologic analysis.
The present study revealed that 73% of surveyed apartments in Moscow whose residents included children with the atopic form of bronchial asthma and sensitization to Dermatophagoides pteronyssinus allergens were infested with the pyroglyphid mites D. pteronyssinus and D. farinae. The number of mites in the surveyed apartments varied between 0 and 154 mites/g of dust for D. pteronyssinus and between 0 and 162 mites/g of dust for D. farinae. The levels of mite allergens in these apartments ranged from 0.5 to 165.8 micrograms/g for Der p I and from 0.3 to 91.3 micrograms/g of dust for Der f I. The Der p I allergen was found to predominate, and its concentration in one-third of the apartments was more than 10-fold greater than that of Der f I. Correlation between the number of pyroglyphid mites and the concentration of group I allergens was established for both D. pteronyssinus (r = 0.4932; P < 0.01) and D. farinae (r = 0.6748; P < 0.01). In most of the apartments, high and moderate levels of Der I allergens were detected.
Animals↗
Sensitization to cockroach allergens of asthma patients in Japan.
To evaluate the role of allergens from Periplaneta fuliginosa, which is the most predominant cockroach species in homes in Tokyo areas, for asthma sensitization, we measured specific IgE antibodies to two cockroaches, P. fuliginosa and Blattella germanica, and to a mite, Dermatophagoides farinae, in 171 sera from children with asthma by Pharmacia's CAP system. We found that 16% of the sera had anti-P. fuliginosa IgE, whereas 9.9% had anti-B. germanica and 85% anti-D. farinae IgE. Further, we measured the levels of Per f I (Per a I equivalent) allergen in the house dust from living room, kitchen and bedding. We detected the allergen in eight of ten homes. The Per a I equivalent levels in kitchen were higher than in other sites, but they were much lower than Der I and Der II as Dermatophagoides allergens.
Allergens↗
Airborne cat (Fel d I), dog (Can f I), and mite (Der I and Der II) allergen levels in the homes of Japan.
We measured the airborne and floor dust allergen levels of the cat (Fel d I), dog (Can f I), and mite (Der I and Der II) allergens in 13 houses. Airborne allergens were sampled with a low-noise air sampler for 5 to 7 days in the living rooms where the inhabitants were living as usual. The mean levels of airborne Fel d I and Can f I in houses with cats or dogs were 5960 and 2880 pg/m3, respectively, which were about 160 and 100 times higher than levels of airborne Der I. In floor dust the mean levels of Fel d I and Can f I were 322 and 236 micrograms/gm fine dust, respectively, which were 59 and 10 times higher than the levels of Der I. These results suggest that the airborne cat and dog allergens might be important sources of allergens for persons who live in a house with those animals, because the absolute allergen levels in both the air and dust are significantly higher than those of mite.
Air↗
The effect of vacuum cleaners on the concentration and particle size distribution of airborne cat allergen.
BACKGROUND: Vacuum cleaners are essential for the removal of dust from the surface of carpets; however, they may also contribute to airborne dust both by leakage through the cleaner and disturbance of floor dust. METHODS: The present studies used established techniques for measuring airborne Fel d I to study the effects of vacuum cleaners on airborne cat allergen under laboratory conditions and in houses with cats. Nine different models were loaded with dust containing 50 mg Fel d I and run for 15 minutes in a laboratory room (volume approximately 18 m3). Leakage was expressed as the airborne concentration of allergen in nanograms per cubic meter. RESULTS: Cleaners incorporating a double-thickness dust bag either did not leak, that is, less than 0.4 ng Fel d I/m3 or had minor leakage approximately 5 ng/m3. Vacuum cleaners with single-thickness paper bags leaked more, that is, 15 to > 90 ng/m3 with the exception of the cleaner with an efficient outer bag. Detailed studies on a vacuum cleaner that leaked showed that placing dust in the bag, replacing the dust bag with a double-thickness bag, and placing an electrostatic filter over the exhaust reduced levels from greater than 90 ng/m3 to less than 2 ng/m3. Two water-filter vacuum cleaners each emitted cat allergen (up to > 100 ng/m3) with a mean of approximately 90% on particles less than 2.5 microns diameter. This emission could be almost completely controlled by taping electrostatic filter paper over the air outlet. CONCLUSIONS: In houses with cats, different models of vacuum cleaners could either reduce or increase total airborne allergen, and could also selectively increase certain particle sizes. These results suggest that cat allergen is a good model for studying the effectiveness of vacuum cleaners recommended to allergic patients.
Air Pollution, Indoor↗
Environmental exposure to Aspergillus fumigatus allergen (Asp f I).
Asp f I is a major allergen produced by the mycelia of Aspergillus fumigatus. It is not present in spores and can be used as a specific marker for the detection of germination of this fungus. We investigated the domestic and outdoor concentration of Asp f I in Poole, U.K. and Charlottesville, VA, U.S.A. Asp f I was undetectable in 95% (281/296) of house dust extracts and present at low levels (< 0.17 micrograms/g of sieved dust, mean 0.038 micrograms/g) in the remainder. In contrast, Asp fI could be detected in 65% (15/23) of cultures of house dust, suggesting the presence of viable, but ungerminated, A. fumigatus in the majority of homes. Asp f I was detectable in 80% (28/35) of extracts of leaves and compost, but present in these outdoor samples at low levels (< 0.11 micrograms/g, mean 0.27 micrograms/g). Air sampling for Asp f I was undertaken before and after vigorous disturbances at indoor (n = 5) and outdoor (n = 6) sites. Airborne Asp f I was not detected in domestic samples or in undisturbed outdoor samples. Following disturbance it could be measured in outdoor samples (range 7.6-29 ng/m3). The results suggest that while exposure to A. fumigatus is common, exposure to Asp f I and germinating A. fumigatus is uncommon. It is probable that those individuals who develop antibody responses to Asp f I have been exposed to A. fumigatus which has germinated in their respiratory tract.
Air↗
Dissecting cockroach allergens.
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Allergens↗
Epitope mapping of the cat (Felis domesticus) major allergen Fel d I by overlapping synthetic peptides and monoclonal antibodies against native and denatured Fel d I.
The major cat allergen Fel d I is a homodimer of which each monomer consists of two disulfide-linked polypeptide chains: chain 1 (70 amino acid residues) and chain 2 (92 amino acid residues). Twenty-one synthetic peptides of 14 amino acid residues length, overlapping by seven residues and spanning the entire sequence of both chains, were synthesized. These peptides were coupled to CNBr-activated Sepharose-4B and used as solid-phase antigens in epitope-mapping studies with monoclonal antibodies against native and reduced/alkylated Fel d I. Two monoclonal antibodies directed against reduced/alkylated chain 1 bound to the overlapping peptides 53-66 and 60-70 of chain 1. The monoclonal antibody directed against reduced/alkylated chain 2 bound to the overlapping peptides 36-49 and 43-56 of chain 2. Binding specificity was demonstrated by inhibition by reduced/alkylated Fel d I for all three monoclonal antibodies. Another monoclonal antibody against reduced/alkylated Fel d I had been found to bind predominantly to reduced/alkylated chain 2 on immunoblot in previous studies. It bound to peptides 1-16 and 60-70 of chain 1 and peptides 1-14 and 50-63 of chain 2; it is therefore probably directed against a conformational epitope formed by these four regions. Possibly because of low affinity of this monoclonal antibody, specificity of its binding could not be verified by inhibition studies. A panel of monoclonal antibodies directed against native Fel d I bound to peptides 1-16 and 60-70 of chain 1 and peptides 1-14 and 43-56 of chain 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkylation↗
Guanine--an adequate index of mite exposure?
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Allergens↗
Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital.
To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room. One hundred and fourteen patients and 114 control subjects were enrolled over a 1-yr period in Wilmington, Delaware. Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen. Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens. IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans. Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 9.4 to 166). For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma. Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen. Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 7.4; confidence interval, 3.3 to 16.5).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗