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Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis.

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. METHODS: Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group. RESULTS: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System). CONCLUSIONS: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.

Adolescent↗

Prevalence and predictors of rhinitis in Danish children and adolescents.

BACKGROUND: The prevalence of self-reported symptoms of allergic rhinitis is increasing in many countries, but the reasons for this trend are not well understood. Data from a 6-year follow-up study of a population sample of children and adolescents (n=408), aged 7-17 years at enrolment in 1986, were analyzed to investigate the prevalence and predictors of self-reported rhinitis. METHODS: Case history was used to assess the presence or absence of rhinitis (sneezing and running or blocked nose not associated with a cold), asthma, and eczema. Pulmonary function, skin prick test reactivity, and airway responsiveness to histamine were measured in all participants; a screening test for IgE antibodies to common allergens (Magic Lite SQ, Allergy Screen, ALK, Denmark) was performed in 237 (58%) of the participants. RESULTS: The point prevalence of rhinitis increased from the first to the second survey, 14% and 22%, respectively; 54 (13%) of the subjects reported rhinitis only at the second survey (new rhinitis). Confining the analysis to participants without symptoms of rhinitis at the first survey showed that self-reported eczema (relative risk [RR] 2.3, 95% confidence interval [CI] 1.2-4.7), airway hyperresponsiveness (RR 2.5, CI 1.8-3.0), atopy to grass pollen (RR 2.6, CI 1.7-3.3), atopy to dog dander (RR 2.4, CI 1.6-3.3), and atopy to house-dust mite (RR 2.7, CI 1.4-5.2) at the first survey predicted an increased risk of the presence of rhinitis at the second survey. A positive Allergy Screen test at enrollment was associated with an increased risk of self-reported rhinitis at follow-up (RR 2.4, CI 1.4-3.4). CONCLUSIONS: This longitudinal population study of children and adolescents showed an age-related increase in the point prevalence of self-reported rhinitis; furthermore, sensitization to common aeroallergens, airway hyperresponsiveness, and the presence of self-reported eczema were significantly associated with an increased risk of subsequent development of rhinitis.

Adolescent↗

Inadvertent BSA-induced elution of IgE in the BSA-RAST.

BACKGROUND: Bovine serum albumin (BSA) is widely used to block nonspecific binding in immunochemical assays. Whereas a previous study had indicated that soluble allergen present during the incubation with anti-IgE in the RAST did not affect bound IgE, we reinvestigated this in the current study, using IgE elution from BSA by soluble BSA as a test system. METHODS: Sepharose-coupled BSA (0.08, 0.4, 2, or 10 microg BSA/test) was incubated overnight with serum and washed. The Sepharose was then incubated with different concentrations of soluble BSA (0, 12, 60, 300, or 1500 microg/test), washed again, and incubated with radioactive anti-IgE. The effect on IgE binding was investigated for various incubation periods (t=0, 1, 2, 4, and 20 h). RESULTS: Incubation in buffer without BSA did not change IgE binding. Soluble BSA eluted IgE antibodies from immobilized BSA by up to 85%. If the BSA density on the solid phase was > or =2 microg/test, the elution efficiency was dependent on the levels of both immobilized BSA and soluble BSA. At lower densities, the dissociation was dependent only on the concentration of soluble BSA. The time needed to obtain 50% IgE elution (t(1/2)) was less if the density of immobilized BSA decreased. Below the critical density (0.8 microg BSA/mg solid phase), t(1/2) was independent of the coating density (45 min). Probably all IgE antibodies are monovalently bound below this density. CONCLUSIONS: Dissociation of IgE from immobilized protein in the presence of soluble protein should be taken into account, particularly when IgE to mammalian serum albumin is involved (milk, meat, or animal dander).

Animals↗

Interleukin-4-positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin.

BACKGROUND: In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin. METHODS: To study the association of tryptase-, chymase-, and interleukin-4 (IL-4)-positive mast cells with the size of the prick-test wheal reaction, 50 sensitive atopic subjects were prick-tested with the cow-dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy-looking skin was biopsied and examined enzyme-histochemically for tryptase and chymase. A double-staining method was used to demonstrate the immunoreactivity of IL-4 and chymase inhibitors (alpha1-proteinase inhibitor and alpha1-antichymotrypsin) in mast cells. The levels of total and cow-specific immunoglobulin E (IgE) were measured in serum. RESULTS: The number of tryptase- and chymase-positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL-4-positive mast cells showed significant positive correlation with the wheal size per se (P<0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control (P<0.003). In addition, tryptase-, chymase-, and IL-4-positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis. CONCLUSIONS: The novel finding was that IL-4-positive, but not tryptase- and chymase-positive, mast cells are intimately associated with the extent of the prick-test wheal.

Adolescent↗

The atopy patch test -- reproducibility and comparison of different evaluation methods.

BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.

Adolescent↗

Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy.

BACKGROUND: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer. CASE REPORT: A 30 year-old female farmer with a long-standing history of grass pollen allergy observed for 2 years rhino-conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent. RESULTS: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)-binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme-linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE-binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE-binding of the tropomyosin control serum was inhibited by 60-80% by all species. CONCLUSIONS: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross-sensitization in the present case was restricted to species of the family of true flies (Muscidae).

Adult↗

Further characterization of IgE-binding antigens from guinea pig hair as new members of the lipocalin family.

BACKGROUND: Guinea pigs are important sources of inhalant allergens in home and working environments. However, little is known about the molecular characteristics and the relevant epitopes of guinea pig allergens. Recently, several allergens have been identified in hair extract and urine, and the major allergen Cav p 1 (20 kDa) has been characterized. OBJECTIVE: The aim of the present study was to isolate and to characterize a further major allergen from guinea pig hair with 17 kDa. METHODS: Guinea pig hair extract was fractionated using anion exchange chromatography and reverse-phase high performance liquid chromatography. Analyses were carried out by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, 2D-PAGE, immunoblotting, immunoblot inhibition, glycoprotein detection, and N-terminal amino acid sequencing. RESULTS: The nonglycosylated 17 kDa allergen, which was named Cav p 2, was purified to homogeneity. On the basis its 15 N-terminal residues, there was 69% identity with a sequence of Bos d 2, an allergenic protein from cow dander belonging to the lipocalin family. The 2D-immunoblotting analyses of guinea pig hair extract demonstrated that Cav p 2 and Cav p 1, contained several isoforms with pI values ranging from 3.6 to 5.3. The 2D-immunoblot inhibition disclosed cross-reactive IgE epitopes on the allergens Cav p 2 and Cav p 1. Furthermore, Cav p 1 can form both monomers (20 kDa) and dimers (40-42 kDa). CONCLUSION: These studies provide important information on the isoallergen character of two relevant guinea pig allergens Cav p 1 and Cav p 2 as well as on their cross-reactive properties.

Allergens↗

Development of immunoglobulin G subclass antibodies to ovalbumin, birch and cat during the first eight years of life in atopic and non-atopic children.

Immune responses to allergens in young children include both Th1- and Th2-like immunity, which may regulate the secretion of immunoglobulin (Ig) G subclass antibodies differently. The time, route and level of exposure to an allergen may be decisive with regard to whether sensitization or tolerance will ensue. To study this, we investigated the development of IgG subclass antibodies to food and inhalant allergens during childhood. The study group comprised a cohort of 96 children participating in a prospective study. IgG subclass antibodies to ovalbumin, Bet v 1 and cat dander were analyzed at birth, 6 and 18 months and 8 years by ELISA. IgG1 and IgG3 subclass antibodies to ovalbumin peaked at 18 months and then declined up to 8 years of age, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increased with age. Exposure to cat and birch tended to be associated with high antibody levels to those allergens, whereas antibody levels to ovalbumin were not related to exposure to egg. The presence of positive skin prick tests and circulating IgE antibodies correlated with high levels of IgG subclass antibody responses to the allergens. Atopic symptoms were associated with high levels of IgG subclass, particularly IgG4, antibodies to the allergens. The difference in antibody levels between atopic and non-atopic children was most marked at 6 months for ovalbumin. For the seasonal inhalant allergen birch, the difference was apparent from 18 months, whereas a difference in antibody levels to the perennial inhalant allergen cat was already present at 6 months. In conclusion, IgG subclass antibodies to food allergens peak in early infancy and are then down-regulated, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increase with age. Atopy is associated with high levels of IgG subclass, particularly IgG4, antibodies to allergens, supporting a deviation of the immune system towards Th2-like responses in atopic children.

Allergens↗

Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events.

Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern, Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren (n=2108) aged 10-11 years from Linköping in southern Sweden and Ostersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in Ostersund and in Linköping. A higher prevalence of sensitization to animal dander among children in Ostersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Linköping (adjusted odds ratio 2.1; 95% confidence interval 1.1-4.0) and in Ostersund (adjusted odds ratio 2.0; 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Linköping, whereas current smoking was associated with a decreased risk of sensitization in Ostersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

Animals↗

Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production.

Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-gamma and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-gamma production was to some extent caused by TGF-beta, as the effect was modified when an anti-TGF-beta antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-gamma production, which was partly due to the high levels of TGF-beta, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-beta in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

Allergens↗

Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects.

In the present study, for the first time, PDE4 subtypes were identified and semi-quantified in both CD4 and CD8 lymphocytes from healthy and asthmatic individuals. CD4 and CD8 lymphocytes from healthy and mild asymptomatic asthmatic subjects (receiving beta-agonist therapy only) were isolated from peripheral venous blood using appropriate antibody coated paramagnetic beads. PDE4 subtypes and beta-actin were identified by digoxigenin (DIG)-labelling reverse transcriptase-polymerase chain reaction and semi-quantified by DIG-detection enzyme-linked immunosorbance assay. In CD4 and CD8 lymphocytes PDE4A, PDE4B and PDE4D were detected, with no significant differences observed between healthy and asthmatic groups. In CD8 lymphocytes, enzyme subtype expression was lower and showed more intersubject variability. In functional studies investigating the effects of various PDE inhibitors on PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects, CDP840 (0.03 - 10 microM), rolipram (0.1 - 10 microM) and theophylline (10 microM - 1 mM) inhibited PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects in a concentration-dependent manner, although no significant difference was observed between the groups investigated. In additional studies, total monocyte cyclic AMP PDE activity was investigated in cells isolated from asthmatic subjects both prior to and 24 h after allergen challenge. Total monocyte cyclic AMP PDE activity remained unaffected following challenge of asthmatic subjects with either house dust mite or cat dander and was inhibited in a concentration-dependent manner by rolipram (0.01 - 100 microM) both before and after allergen challenge.

3',5'-Cyclic-AMP Phosphodiesterases↗

The relationships between personal PM exposures for elderly populations and indoor and outdoor concentrations for three retirement center scenarios.

Personal exposures, indoor and outdoor concentrations, and questionnaire data were collected in three retirement center settings, supporting broader particulate matter (PM)--health studies of elderly populations. The studies varied geographically and temporally, with populations studied in Baltimore, MD in the summer of 1998, and Fresno, CA in the winter and spring of 1999. The sequential nature of the studies and the relatively rapid review of the mass concentration data after each segment provided the opportunity to modify the experimental designs, including the information collected from activity diary and baseline questionnaires and influencing factors (e.g., heating, ventilation, and air-conditioning (HVAC) system operation, door and window openings, air exchange rate) measurements. This paper highlights both PM2.5 and PM10 personal exposure data and interrelationships across the three retirement center settings, and identifies the most probable influencing factors. The current limited availability of questionnaire results, and chemical speciation data beyond mass concentration for these studies, provided only limited capability to estimate personal exposures from models and apportion the personal exposure collections to their sources. The mean personal PM2.5 exposures for the elderly in three retirement centers were found to be consistently higher than the paired apartment concentrations by 50% to 68%, even though different facility types and geographic locations were represented. Mean personal-to-outdoor ratios were found to 0.70, 0.82, and 1.10, and appeared to be influenced by the time doors and windows were open and aggressive particle removal by the HVAC systems. Essentially identical computed mean PM2.5 personal clouds of 3 micrograms/m3 were determined for two of the studies. The proposed significant contributing factors to these personal clouds were resuspended particles from carpeting, collection of body dander and clothing fibers, personal proximity to open doors and windows, and elevated PM levels in nonapartment indoor microenvironments.

Aerosols↗

New insights into the relationship between airway inflammation and asthma.

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.

Asthma↗

Changes in IgE-mediated allergy to ubiquitous inhalants after removal from or diminution of exposure to the agent causing occupational asthma.

BACKGROUND: One possibility, among others, for explaining the persistence of asthma symptoms in occupational asthma (OA) after the cessation of exposure to the causal agents may be that subjects become sensitized to ubiquitous inhalants. OBJECTIVE: The aim of this study was to evaluate the development or increase of IgE-mediated sensitization to ubiquitous allergens, both to high- and low-molecular-weight agents, in 100 subjects with OA after cessation of exposure. METHODS: Subjects were evaluated on a first visit, at the time of diagnosis of OA, coinciding with the cessation or diminution of exposure to the causal agent, and on a second visit, 5.8+/-3.3 years afterwards. At each visit, a history of ocular, nasal and asthmatic symptoms related to exposure to common allergens was obtained together with spirometry and assessment of bronchial responsiveness to methacholine. We analysed total IgE and specific IgE to Dermatophagoides farinae, D. pteronyssinus, birch, ragweed and timothy grass pollens, cat and dog danders, and Alternaria, using enzyme allergosorbent test (EAST) from blood samples taken on each visit. RESULTS: Total IgE levels showed a tendency to diminish. No changes were found in the number of positive EAST (presence of detectable levels of specific IgE) or in the levels of specific IgE. Although significantly more symptoms of rhinoconjunctivitis and asthma in contact with house dust (P < 0.05) and pets (P < 0.01) were reported on the second visit than on the first, no significant changes in the frequency of symptomatic sensitized subjects were found. CONCLUSION: Subjects with OA are unlikely to develop IgE-dependent sensitization to common inhalants after removal from exposure to occupational agents.

Adult↗

Epidemiology of insect venom sensitivity in children and its correlation to clinical and atopic features.

The aim of this study was to obtain more accurate figures of the prevalence of cutaneous sensitivity to Hymenoptera venoms (HV) and its correlation with other parameters of atopy in a population of primary schoolchildren. Parents filled out a structured questionnaire and children were tested with a panel of inhalant and food allergens as well as standardized freeze-dried extracts of HV. Among the 1175 children who completed the study there was a personal history of rhinoconjunctivitis in 242 (20.8%) and a current wheezing in 114 (9.78%). Two-hundred twenty-eight (19.40%) children had a history of Hymenoptera sting (HS) reactions (224 or 19.06% of local reactions and 4 or 0.34% of local and systemic reactions). Positive skin-prick tests (SPT) to any given HV extract were present in 43 children (3.66%). Most subjects had positive SPT to honey bee venom (35/1175; 2.98%); 17/1175 (1.45%) had positive SPT to wasp and only 12 subjects (1.02%) had positive SPT to polistes venom. There was a correlation between a positive SPT to HV and the history of clinical reactions to HS (P=0.0026). Positive SPT to at least one of the inhalant and food allergens tested were found in 353 subjects (30.04%). Factors such as age, sex, reactions to HV, positive SPT to mite, cat dander, grass, Alternaria, Parietaria, cow's milk, egg white and wheat were significantly associated with a positive SPT to HV using a univariate regression analysis. Only age, reactions to HV, a positive SPT to grass, Parietaria, cow's milk, and egg white were significantly associated with a positive SPT to HV using a multiple regression analysis. In this study, the frequency of immunological sensitization to HV in a population of unselected children is not so high as in adults. There is an association between the presence of positive SPT to HV and an atopy linked humoral IgE response. The presence of a significant and independent association between positive SPT to food of animal origin and positive SPT to HV is surprising and needs further study.

Animals↗

High prevalence of sensitization to cat allergen among Japanese children with asthma, living without cats.

BACKGROUND: Cat allergy is common among children with asthma. Many cat-allergic patients in Japan and elsewhere do not keep cats, but nonetheless become sensitized through environmental exposure to cat allergen. OBJECTIVE: To assess the frequency of cat allergy and cat-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody responses in young Japanese patients with asthma in relation to self-reported cat exposure and Fel d 1 levels in dust samples. METHODS: Cat dander-specific IgE antibody was measured in sera from asthma patients using the CAP system. IgE and IgG antibody to Fel d 1 was measured by antigen binding radioimmunoassay and by chimeric enzyme immunoassay. Fel d 1 levels in dust samples from a subset of patients' homes were measured by monoclonal antibody-based enzyme immunoassay. RESULTS: Cat-specific IgE (CAP class>/=2) was found in sera from 70% of 44 patients who kept cats and 34% of 394 patients who had never kept cats. The prevalence of sensitization increased progressively to age 6 years (40%: positive), and then increased gradually to age 16 years (approximately 60%: positive) in patients who had never kept cats. There was an excellent correlation between cat CAP values and IgE levels to Fel d 1. The absolute amount of IgE antibody to Fel d 1 ranged from 0.01 to 15.6% of total IgE. Most patients who did not keep cats were exposed to Fel d 1 levels ranging from 0.07-8 microg/g dust. CONCLUSIONS: Sensitization to cat allergen is common among young asthmatic patients in Japan, even among patients who do not keep cats. Use of CAP and the chimeric enzyme-linked immunosorbent assay allows accurate diagnosis of cat allergy and quantification of specific IgE antibody levels.

Adolescent↗

Relationship between allergic status and specificity of IgG antibody to inhaled allergens: the grass pollen model.

BACKGROUND: We have previously reported that IgG antibodies from healthy individuals and patients suffering from non-seasonal mite allergy bind to different sets of epitopes on Der p 1, allowing almost complete discrimination of the populations. OBJECTIVES: To confirm this observation in a seasonal allergy model where a clear relationship between allergic symptoms and exposure to the offending agent is established. To investigate whether the pattern of modified specificity is related to the differences in IgG subclass hierarchy usually exhibited by nonallergic and allergic populations. METHODS: The capacity of individual sera from patients allergic to grass pollen and healthy individuals, including grass pollen-sensitized subjects, to prevent the binding of pooled IgG, IgG1, and IgG4 fractions from grass pollen-allergic patients and healthy individuals to solid-phase bound grass pollen antigen was evaluated in enzyme-linked immunosorbent assay (ELISA) using streptavidin-biotin technology. Specificity controls were performed using sera from patients allergic to cat dander and house dust mite. RESULTS: The capacity of sera to prevent the antigen binding of allergic IgG averaged 84 +/- 5% for allergic sera and 53 +/- 6% for healthy sera (P < 0.001 by one-way anova). Conversely, using the antigen-binding capacity of healthy control IgG as reference, percentage inhibitions averaged 46 +/- 9% in grass pollen-allergic subjects compared with 80 +/- 4%, 82 +/- 2% in healthy individuals, and mite- and cat-allergic patients, respectively, resulting in two well-separated populations (P < 0.0001 by one-way anova). Similar results were found regardless of whether pooled IgG1 or IgG4 were used. CONCLUSION: Together with previous data, our results define a new type of humoral signature in the immune response to inhaled allergens. Allergic and healthy status differ not only in the presence or absence of specific IgE antibody but also in the preferential expression of distinct IgG specificities that are better correlated with clinical manifestations and are unrelated to subclass distribution.

Adult↗

Genetic linkage of HLA-class II locus to mite-specific IgE immune responsiveness.

BACKGROUND: IgE response to common inhalant allergens seems to be the major determinant of the development of atopic rhinitis and asthma but it has been difficult to demonstrate genetic control of the IgE response. OBJECTIVE: To investigate genetic linkage between specific IgE reactions to purified aero-allergens (grass, birch, cat, mite) and the HLA-class II locus. METHODS: DNA-based HLA-class II typing was performed for determination of DRB1, DQB1 and DPB1 alleles. Linkage was studied by the affected sibpair method and the extended transmission disequilibrium test in 100 children from 40 nuclear families selected from a homogeneous population in south-western Germany. RESULTS: Significant linkage of mite-specific IgE response to HLA-DPB (P = 0.00001), HLA-DRB (0.02) and HLA-DQB (P = 0.001) was revealed by sibpair analysis of MHC class II alleles and confirmed by the extended transmission disequilibrium test for HLA-DRB (P = 0.01) and HLA-DPB (P = 0.04). No consistent significant linkage between the HLA-class II locus and IgE response to grass pollen, birch pollen, and cat dander could be demonstrated. CONCLUSION: The findings are consistent with the existence of one or more genes in the HLA-class II region modifying the IgE immune response to common environmental allergens.

Adolescent↗