Increased incidence of skin infections in atopy: evidence for an antigen-specific homing defect?
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Animals↗
Biomedical subjects
T A Platts-Mills
Publications and source records attributed to T A Platts-Mills.
Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: delayed-type hypersensitivity-associated major epitopes induce Th1- and Th2-dominated responses.
Distinct immune responses in humans to the Trichophyton rubrum Ag, Tri r 2, are associated with different patterns of T cell epitope recognition based on in vitro proliferation to peptides derived from this 29-kDa protein. Specifically, the amino-terminal immunodominant epitope, peptide 5 (P5), stimulates strong T cell proliferative responses in subjects with delayed (DTH), but not immediate (IH) hypersensitivity skin tests. Evidence of a role for cytokines or changes in epitope recognition over time was examined in responses to Trichophyton using primary PBMC cultures established from seven IH and seven DTH subjects. Responses stimulated by Tri r 2 were dominated by the Th1 cytokine IFN-gamma (IFN-gamma:IL-5 > or = 4:1) in five DTH subjects, even in the presence of Th2-dominated responses (IFN-gamma:IL-5 < or = 3:1) to a subset of major epitopes. Paradoxically, P5 induced IL-5 and IL-10 production in DTH, but not IH subjects (p = 0.003 (IL-5), p = 0.024 (IL-10)), with no significant difference in IFN-gamma levels between the two groups. In cultures from IH responders, no IL-5 was measurable after stimulation with P6 and P7 (as well as P5); this region of the molecule was shown previously to stimulate markedly reduced T cell proliferation in these individuals. Repeat proliferation assays confirmed no change in the pattern of peptide recognition after > or =20 mo in IH or DTH subjects. We conclude that T cell repertoires associated with distinct immune responses to Tri r 2 can be distinguished based on Th2 cytokine induction by DTH-associated major epitopes localizing to the amino-terminal region of the molecule.
Adult↗
The role of immunoglobulin E in allergy and asthma.
It has been nearly a century since the first suggestion that a soluble factor in plasma or serum might be responsible for the symptoms of allergic disease and asthma, and more than 30 yr since immunoglobulin E (IgE) was identified as the key molecule in mediating what are now described as type 1 hypersensitivity reactions (allergic asthma, allergic rhinitis, food allergy, atopic dermatitis, some forms of drug allergy, and insect sting allergy). Since that time, many of the details of the inflammatory cascade underlying allergy and asthma have been elucidated, and IgE is now known to play a key upstream role. The goals of this report are to review the cellular and molecular events set in motion by IgE and to examine the evidence for its participation in both the immediate allergic response and the late-phase or chronic inflammatory response in the skin and lungs.
Asthma↗
Con: the increase in asthma cannot be ascribed to cleanliness.
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Asthma↗
Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.
Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30-60 minutes. One asthmatic subject was studied twice in a three-week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy.
Adult↗
Chronic dermatophytosis in lamellar ichthyosis: relevance of a T-helper 2-type immune response to Trichophyton rubrum.
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Chronic Disease↗
IgE and IgG antibody responses to recombinant Alt a 1 as a marker of sensitization to Alternaria in asthma and atopic dermatitis.
BACKGROUND: Sensitization to Alternaria alternata is a risk factor for the development of wheezing and asthma. Alt a 1 is the major Alternaria allergen causing sensitization in asthmatics. Some atopic dermatitis (AD) patients have very high immunoglobulin (Ig)E antibody (ab) to Alternaria as analysed by Pharmacia CAP, however, it is not clear whether these are specific responses or whether Alt a 1 is involved in disease symptoms. OBJECTIVE: The aim of this study was to analyse specific IgE and IgG ab responses to recombinant Alt a 1 in asthmatic and AD patients and to compare these results to IgE ab against Alternaria measured by CAP. METHODS: Sera from individuals who were IgE positive to Alternaria by CAP were obtained from 58 patients with asthma/rhinitis, 19 patients with AD, and 20 patients with cystic fibrosis (CF) who were included as specificity controls. IgE and IgG ab to recombinant Alt a 1 were measured by radioimmunoassay (RIA). RESULTS: Of 43 asthma/rhinitis patients having an Alternaria CAP score > 2, a high percentage (93%) had both IgE and IgG ab to Alt a 1, emphasizing its importance as a major allergen. Only, 47% of AD patients with CAP score greater than 2 had ab to Alt a 1, and their levels were low when compared to the asthmatics. For CF controls, 75% of these patients had no IgE ab to Alt a 1, and those which were positive to Alt a 1 by RIA were also positive by CAP. Overall, patients with a low CAP (1-2) had a low prevalence (20-30%) of IgE or IgG ab to Alt a 1. CONCLUSION: IgE and IgG ab to Alt a 1 in asthmatics are good markers for sensitization to Alternaria. Although AD patients gave high Alternaria CAP scores, they had low or undetectable levels of IgE to Alt a 1, suggesting that other Alternaria allergens may be important in AD or that the CAP results are non-specific. Recombinant allergens may provide more specific measures of sensitization to fungi.
Allergens↗
Association of specific allergen sensitization with socioeconomic factors and allergic disease in a population of Boston women.
BACKGROUND: Socioeconomic differences in allergic disease prevalence have been reported; asthma has been associated with poverty in the United States and hay fever and eczema with relative affluence elsewhere. It is not yet established to what degree such differences in disease prevalence reflect patterns of sensitization and specific allergen sensitivities. OBJECTIVE: We analyzed specific and total IgE measurements in a sample of 458 women, enriched for allergic disease, from the metropolitan Boston area to establish the relation of allergen sensitization to markers of socioeconomic status (SES) and to the prevalence and socioeconomic pattern of allergic disease in this community. METHODS: Total and specific IgE antibodies were measured with the UNICAP System; self-reported allergic disease, household income, education, and race-ethnicity were ascertained with a questionnaire; and a further marker of poverty (percentage living below the poverty level) in the women's area of residence was established on the basis of zip codes. Analysis was performed with SAS statistical software. RESULTS: Markers of low SES were univariately associated with increases in total IgE, number of allergen sensitizations, and levels of specific IgE. Socioeconomic differences in sensitization to cockroach (35% vs 6% in the highest and lowest poverty areas), animal (44% vs 26%), and ragweed (49% vs 23%) allergens were most marked. Sensitization primarily to indoor inhalant allergens (not ragweed or ryegrass) were associated with an increased risk of asthma, even after adjustment for SES. CONCLUSION: We have demonstrated a socioeconomic gradient in sensitization that concords with increased rates of asthma in less affluent communities in this population.
Adolescent↗
The biology of dust mites and the remediation of mite allergens in allergic disease.
In most temperate humid areas of the world, house dust mites are a major source of multiple allergens in house dust. Mite allergens sensitize and induce perennial rhinitis, asthma, or atopic dermatitis in a large portion of patients with allergic disease. There is convincing evidence that avoidance of mite allergen can effectively reduce allergic symptoms. Patients can be moved to a mite allergen-free environment, or mite and mite allergen abatement can be performed to reduce exposure in existing residences. Some knowledge of the biology of house dust mites is essential to understand the basis of the recommendations for reducing mites and mite allergens in homes and to appreciate the difficulty of eliminating house dust mites and mite allergens from homes. This article reviews key aspects of the biology of dust mites, the properties of mite allergens, recommendations for reducing mite and mite allergen concentrations in homes, and practical recommendations for treatment.
Allergens↗
Home intervention in the treatment of asthma among inner-city children.
BACKGROUND: In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty. OBJECTIVE: We sought to investigate allergen avoidance as a treatment for asthma among inner-city children. METHODS: One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels. RESULTS: There was a significant decrease in acute visits for asthma among children whose homes were visited (P < .001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P < .01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits. CONCLUSIONS: Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.
Adolescent↗
Detection of IgA and IgG but not IgE antibody to respiratory syncytial virus in nasal washes and sera from infants with wheezing.
BACKGROUND AND OBJECTIVE: The capacity of respiratory syncytial virus (RSV) to stimulate an IgE antibody response and enhance the development of atopy and asthma remains controversial. Nasal washes and sera from 40 infants (20 with wheezing, 9 with rhinitis, and 11 without respiratory tract symptoms) were obtained to measure IgE, IgA, and IgG antibody to the immunodominant, F and G, virion proteins from RSV. STUDY DESIGN: Children (aged 6 weeks to 2 years) were enrolled in the emergency department during the mid-winter months and seen at follow-up when they were asymptomatic. All nasal washes were tested for RSV antigen. Determinations of antibody isotypes (IgE, IgA, and IgG) to RSV antigens were done in nasal washes and sera by using an enzyme-linked immunosorbent assay. In a subset of nasal washes, IgE to RSV was also evaluated by using a monoclonal anti-F(c)E antibody-based assay. RESULTS: Fifteen patients with wheezing, two with rhinitis, and one control subject tested positive for RSV antigen at enrollment. Thirteen patients with wheezing were <6 months old, and most (77%) were experiencing their first attack. Among the children with positive test results for RSV antigen, an increase in both nasal wash and serum IgA antibody to RSV-F(a) and G(a) was observed at the follow-up visit. However, there was no evidence for an IgE antibody response to either antigen. CONCLUSION: Both IgA and IgG antibodies to the immunodominant RSV-F(a) and G(a) antigens were readily detected in the nasal washes and sera from patients in this study. We were unable to demonstrate specific IgE antibody to these antigens and conclude that the production of IgE as a manifestation of a T(H)2 lymphocyte response to RSV is unlikely.
Antigens, Viral↗
Decreased prevalence of asthma among children with high exposure to cat allergen: relevance of the modified Th2 response.
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Allergens↗
Allergen exposure and the development of asthma.
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Allergens↗
Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2.
The 29-kDa subtilase homologue, Tri r 2, derived from the dermatophyte fungus Trichophyton rubrum, exhibits unique immunologic characteristics in its ability to elicit immediate (IH) and delayed-type (DTH) hypersensitivity skin tests in different individuals. Thus, Tri r 2 provides a model for comparing the T cell repertoire in subjects with distinct immune responses to a single Ag. Recombinant Tri r 2 produced as a GST fusion protein in Escherichia coli stimulated strong in vitro lymphoproliferative responses in 10 IH and 10 DTH responders. Patterns of T cell epitope recognition were compared between skin test groups using 28 overlapping peptides (each in 12 replicate wells) derived from Tri r 2 to stimulate T lymphocyte proliferation in vitro. Peptide 5 (P5; aa 41-60) induced the strongest response in DTH subjects and showed the largest difference between DTH and IH responders in proliferation (mean standardized index, 2.22 and 0.82, respectively; p = 0.0047) and number of positive wells (81 vs 12). Responses to P5 were associated with diverse HLA haplotypes. These results showed that P5 contains an immunodominant epitope specifically associated with DTH and that this peptide is recognized in a permissive manner. Cross-validated linear discriminant analysis using T cell proliferative responses to two regions of Tri r 2 (aa 51-90 and 231-270) gave a 95% predictive accuracy for classification of subjects into IH or DTH groups. We conclude that different immune responses to Trichophyton are mediated by distinct T cell repertoires between individuals with IH and DTH reactions to Tri r 2.
Adult↗
A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.
BACKGROUND: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy. METHODS: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks. RESULTS: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse. CONCLUSIONS: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity.
Adrenal Cortex Hormones↗
Salivary cotinine levels in children presenting with wheezing to an emergency department.
We set out to evaluate salivary cotinine concentrations to judge tobacco smoke exposure among infants and children, and to examine the results in relation to age and wheezing. This was a case-control study of wheezing children (n = 165) and children without respiratory tract symptoms (n = 106) who were enrolled in the Pediatric Emergency Department at the University of Virginia. The age range of both wheezing and control patients was 2 months to 16 years. Questionnaires were combined with cotinine assays in saliva to evaluate exposure to environmental tobacco smoke (ETS) for each child. The prevalence of exposure to one or more smokers at home was high (68%); and 43% of the children enrolled were exposed to ETS from their mothers. According to the questionnaires, and after adjusting for age and race, a wheezing child in this study was more likely than a control to be exposed to at least one smoker at home (odds ratio = 1.9; 95% CI = 1.1-3.4). However, the odds of exposure to ETS from smoking mothers did not differ significantly between wheezing and control patients, and no significant association was found between the presence of wheezing and salivary cotinine levels. Among children exposed to ETS at home, cotinine levels were significantly higher in saliva from those under the age of two years, and from toddlers aged 2 and 3 years, compared to values from children over age 4 years. Moreover, the number of smokers in the home strongly influenced cotinine levels from children under age 4 years. In addition, higher cotinine levels were observed in saliva from children under age 2 years who were exposed to ETS from their mothers. Cotinine levels were similar and significantly correlated in paired samples of saliva and serum from children under 4 years of age (n = 54), (r = 0.92, P < 0.001). Based on information gathered from questionnaires, the results indicate that wheezing children were more likely than controls to be exposed to ETS at home. However, significant differences in ETS exposure between wheezing and control groups with respect to maternal smoke exposure or comparisons of salivary cotinine levels were not apparent. It was clear that determinations of salivary cotinine for monitoring the prevalence and intensity of household smoke exposure in this study were most valuable during the first 4 years of life.
Adolescent↗
The relevance of allergen exposure to the development of asthma in childhood.
Sensitization to 1 or more of the common indoor allergens has been consistently associated with asthma among children and young adults (odds ratios for asthma, 3-18). For dust mite and cockroach allergens, there is a dose response relationship between domestic exposure and sensitization. Given that allergen provocation can induce many of the features of asthma, the findings strongly suggest that there is a causal relationship between allergen exposure in the home and asthma. However, it remains unclear at what time the critical exposure occurs (ie, in infancy or later) and what role allergen exposure has played in the increasing prevalence and severity of asthma. Objective evidence of an immune response to allergens is generally not present until after 2 years of age. Viral infections play several different roles in asthma in childhood. In infancy, respiratory syncytial virus infection can induce bronchiolitis and set up recurrent wheezing over the next few years. However, the risk factors for this are maternal smoking and small lungs at birth, rather than allergy. By contrast, the role of rhinovirus in precipitating attacks in children and young adults is strongly associated with allergy. Thus the likely scenario is that allergen exposure over the first few years of life induces sensitization (ie, T(H2) cells and IgE antibodies). Continuing exposure can maintain inflammation in the nose and lungs. However, many other factors contribute to wheezing such that there is no simple relationship between allergen exposure and asthma. Nonetheless, it is clear that the changes that have increased asthma have acted on allergic children.
Allergens↗
Quantitative IgE antibody assays in allergic diseases.
During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.
Antibodies, Anti-Idiotypic↗