bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ cells proliferate after peanut‐extract‐specific and CD8+ cells proliferate after polyclonal stimulation of PBMC of children with atopic dermatitis
Authors: Laan  , Tibbe  , Oranje  , Bosmans  , Neijens  , Savelkoul  
Published: March 2003

BackgroundFew studies describe in vitro food‐allergen induced proliferative responses and cytokine production of PBMC of children with atopic dermatitis. This is especially true for peanut‐allergen.ObjectivesTo analyse the specificity of the T cell in proliferative responses, in children with atopic dermatitis with or without peanut allergy and healthy age‐matched children.MethodsProliferative responses were measured by [3H]‐thymidine incorporation and by expression of the intracellular Ki67‐antigen using flow cytometry after antigen‐specific stimulation of PBMC with peanut‐extract (day 7) or polyclonal stimulation with Phorbol‐12myristate‐13acetate and Ca‐ionophore (day 3). Cytokine mRNA (Interferon‐gamma (IFNγ), IL‐4) was detected by semiquantitative RT‐PCR. Cytokine production (IL‐4, IFNγ) was measured by ELISA.ResultsPeanut‐extract induced proliferative responses of PBMC from children with atopic dermatitis and peanut allergy (AD+PA+) were significantly higher as compared with the other groups studied. Ki67‐antigen double staining revealed that 80–100% of the proliferating cells were CD4+. These proliferative responses correlated significantly with the increase in IL‐4 mRNA expression after peanut‐extract specific stimulation. After polyclonal stimulation, however, CD8+ cells preferentially proliferated. The degree of proliferation after polyclonal stimulation correlated inversely with the ratio of IL‐4/IFNγ production.ConclusionsThe principal responding population of T cells in proliferative responses is different after peanut‐extract specific and polyclonal stimulation of PBMC from AD+PA+ patients. Furthermore, we found indirect evidence that the PBMC fraction of AD+PA+ children contains increased frequencies of peanut‐specific T helper‐2 cells.
The frequency and clinical significance of specific IgE to both wasp (Vespula) and honey‐bee (Apis) venoms in the same patient
Authors: Egner  , Ward  , Brown  , Ewan  
Published: March 2003

BackgroundChangeover from Phadebas RAST to Pharmacia AutoCAP increased double‐positivity to both honey‐bee and common wasp (vespula) venom in our patients.ObjectiveWe examined the frequency of IgE double‐positivity, its clinical relevance and utility in investigating potentially allergic patients.MethodsOne hundred and eighty‐two patients with hymenoptera allergy were tested using RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history of reactions to vespulae (22), honey‐bee (10) and unidentified hymenoptera (vespinae) (7).ResultsAfter changing from RAST to AutoCAP double‐positivity increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave similar median class results (vespula = 3, honey‐bee = 2). Thirty‐six CAP patients had systemic reactions of Mueller grade II and above. In vespula‐allergic double‐positive subjects, high CAP classes ( class 3) to honey‐bee were common (30%). In 25% the CAP classes were equal. In honey‐bee‐allergic subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were equal for both venoms. In 43% of vespinae‐allergic patients the CAP class was equal to both (class 2 and 3). In contrast, intradermal skin test double‐positivity was uncommon. Double‐negative skin test results were common in the CAP double‐positive population (22% of honey‐bee‐allergic, 13% of vespula‐allergic and 43% of vespinae‐allergic patients). Vespula allergic patients have higher bee‐venom IgE than vice versa. Twenty‐seven per cent of CAP double‐positive patients (representing 8% of all venom allergic patients tested over this period) had equal class IgE to both venoms which was not helpful in diagnosis. Combination of skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double‐positive serology.ConclusionIf used in isolation CAP may be misleading, especially if only one venom is tested. Identification of the causative venom must utilize both clinical history and skin testing in these double‐positive patients, and challenge testing if indicated.
Serum eosinophil cationic protein, eosinophil protein X and eosinophil peroxidase in relation to pulmonary function in cystic fibrosis
Authors: Koller D. Y. , Nilsson M. , Enander I. , Venge P. , Eichler I. 
Published: March 2003

BackgroundRecently, increased serum levels of eosinophil cationic protein (ECP) in cystic fibrosis (CF) have been reported which were closely related to the levels in sputum. In the present study we investigated other eosinophil proteins such as eosinophil peroxidase (EPO) and eosinophil protein X (EPX) in sera of patients with CF and their relation to pulmonary function.MethodsSerum samples from 42 patients with CF and from 25 healthy control subjects were measured for ECP, EPO and EPX. Lung function tests were performed by using whole body plethysmographic technique, and the results were correlated with the levels of eosinophil granule proteins.ResultsSerum ECP (median: 20.9 μg/L), EPO (median: 30.3 μg/L) and EPX (median: 37.9 μg/L) levels were significantly increased in CF compared with healthy controls (3.5 μg/L, P < 0.0001, 5.6 μg/L, P < 0.0001 and 14.6 μg/L, P < 0.0001, respectively) whereas eosinophil counts were not different. There was a strong correlation between the levels of eosinophil proteins and variables of pulmonary function, like between ECP and forced vital capacity (r = − 0.764, P < 0.0001). In addition, ECP concentrations were significantly related to the levels of EPO and EPX, albeit, in some patients with low ECP levels, increased EPO and EPX concentrations were observed.ConclusionThese results indicate that in patients with CF, ECP, EPO and EPX concentrations also were increased with a significant relationship between these three eosinophil proteins. Since eosinophil activity in patients with CF is strongly correlated with pulmonary function, the assessment of eosinophil granule proteins might be useful for clinical monitoring in CF.
Heat shock protein 70 upregulation is related to HLA‐DR expression in bronchial asthma. Effects of inhaled glucocorticoids
Authors: Bertorelli  , Bocchino  , Zhuo  , Chetta  , Del Donno  , Foresi  , Testi  , Olivieri  
Published: March 2003

Background and objectiveAntigen processing determines the production of peptides from antigens — including allergens — and their binding to class II major histocompatibility complex molecules, that stimulate T‐cell responses. Heat shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic peptides and in facilitating class II peptide assembly. We studied the HLA‐DR and hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as the effect of low dose fluticasone propionate treatment.MethodsTwenty‐three asthmatics and eight normal subjects were selected. In each subject BAL and bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 μg bd) in a placebo‐controlled double‐blind study. BAL fluid and biopsies were processed to evaluate HLA‐DR and hsp70 expression by immunochemistry methods.ResultsHsp70 and HLA‐DR upregulation was present on professional and non‐professional antigen presenting cells (APCs). In asthmatics, the hsp70 and HLA‐DR expression was higher in BAL (hsp70 P < 0.001, HLA‐DR P < 0.001) and bronchial epithelium (hsp70 P < 0.001, HLA‐DR P < 0.001) when compared with controls. We also observed a significant correlation between hsp70 and HLA‐DR expression in BAL (P < 0.005) and epithelium (P < 0.001). Fluticasone propionate treatment down‐regulated the hsp70 and HLA‐DR expression in BAL (hsp70 P < 0.001, HLA‐DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA‐DR P < 0.05). A serial section comparison study showed that CD1a+ cells and macrophages were positive for both hsp70 and HLA‐DR in the submucosa.ConclusionsOur results support the hypothesis that hsp70 over‐expression implies a potential role for these proteins in antigen processing and/or presentation resulting in an increased activity of APCs, which is essential for the initiation and modulation of the asthmatic immune response in chronic asthma. Fluticasone propionate induces down‐regulation of HLA‐DR and hsp70 molecules thus regulating inflammation by affecting key mechanisms of the allergic response.
Inhalant allergy to egg yolk and egg white proteins
Authors: Quirce  , DÍez‐GÓmez  , Eiras  , Cuevas  , Baz  , Losada  
Published: March 2003

BackgroundSeveral egg white and egg yolk and avian proteins have been described as a cause of inhalant allergy. Sometimes inhalational type I hypersensitivity to these proteins is associated with food allergy to egg.ObjectiveWe studied two patients who experienced respiratory and food allergic symptoms upon exposure to egg or avian antigens through the inhalative or digestive routes. Clinical and immunological studies were carried out in order to identify individual allergens from these sources that could be responsible for crossreactivity reactions.ResultsPatient 1 showed IgE sensitization to egg yolk livetins, feathers, and chicken serum. Specific bronchial challenge with chicken albumin and livetin extracts elicited a positive early asthmatic response and an increase in serum eosinophil cationic protein. Immunoblot and CAP‐inhibition studies in this patient supported that chicken albumin (α‐livetin) was the crossreactive antigen present in egg yolk and chicken serum and feathers. Patient 2 showed sensitization to egg white, ovomucoid and lysozyme. However, SDS‐PAGE and immunoblot studies demonstrated contaminating lysozyme in the ovomucoid extract and identified lysozyme as the main allergen causing egg sensitization in this patient. Conjunctival challenge test confirmed allergy to lysozyme.ConclusionEgg yolk and egg white proteins may act not only as ingested allergens but also as aeroallergens. Immunological studies using highly purified preparations of egg proteins are useful for the accurate diagnosis of allergic reactions to egg proteins and to identify individual allergens that may be responsible for crossreactivity reactions.
Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma
Authors: Albuquerque  , Hayden  , Palmer  , Laing  , Rye  , Gibson  , Burton  , Goldblatt  , LesouËF  
Published: March 2003

BackgroundTumour necrosis factor alpha (TNFα) is a potent modulator of immune and inflammatory responses, and has been implicated in a variety of autoimmune diseases, including asthma. Increased levels of TNFα have been detected in both sputa and bronchoalveolar lavage fluid of asthmatic subjects during acute attacks. Interindividual variation in TNFα levels may be genetically determined and polymorphisms within the TNF genes and nearby HLA Class II region have been associated with differences in TNFα production. Objective To investigate the association of differences in asthma‐related phenotypes with two biallelic polymorphisms: a G to A substitution at position −308 of the TNFα gene promoter (TNF1 and TNF2 alleles) and an NcoI polymorphism in the first intron of the lymphotoxin alpha gene (LT‐α*1 and LT‐α*2 alleles).MethodsThe regions of interest were amplified from genomic DNA using specific primers and PCR. Dot blot analysis was used for genotyping individuals for the TNFα− 308 polymorphism, while restriction enzyme digestion was used for genotyping individuals for the LT‐α gene NcoI polymorphism. A case‐control analysis was then performed on 74 asthmatic and 50 non‐asthmatic unrelated children for each polymorphism.ResultsThe TNFα−308 TNF1 allele was present at a significantly higher frequency in cases than controls (OR = 2.4, P = 0.003), and homozygosity for the TNF1 allele was associated with a fivefold increased risk of physician diagnosed asthma relative to the other genotypes (OR = 5.23, P = 0.004). The LT‐α*2 allele showed similar associations, including an approximately fivefold higher risk of physician diagnosed asthma for LT‐α*2 homozygotes (OR = 4.89, P = 0.019). Evidence of a significant linear trend in asthma risk across the three genotypes was found for both polymorphisms.ConclusionThese results suggest an important role for the TNFα gene or a linked locus in an inherited asthma diathesis.
Atopic dermatitis in early infancy predicts allergic airway disease at 5 years
Authors: Bergmann  , Edenharter  , Bergmann  , Forster  , Bauer  , Wahn  , Zepp  , Wahn  
Published: March 2003

BackgroundScreening tests for atopy risk in newborns have a low predictive value. If early atopic symptoms and signs could be used as predictors for the next expected atopic disorder then secondary prevention could be employed. The aim of this study was to evaluate the capacity of early atopic dermatitis to predict aeroallergen sensitization and the manifestation of respiratory atopic disorders at 5 years of age.Methods1314 children of a German prospective birth cohort study MAS‐90 were followed from birth up to 5 years of age. Atopic dermatitis, asthma and rhinoconjunctivitis were diagnosed from symptoms and signs at physical examinations and by interviews of the parents. Blood was drawn at 1, 2, 3, and 5 years of age. Aeroallergen sensitization was diagnosed by a specific IgE value of at least 0.35 kU/L (CAP class ≥ 1) against any of five respiratory allergens (mite, cat, dog, birch, grass).ResultsAtopic dermatitis in the first 3 months was a risk factor for aeroallergen sensitization at 5 years. The risk increased with a positive family history for atopic diseases. Seventy‐seven per cent of children with two atopic parents and early atopic dermatitis were sensitized against aeroallergens at 5 years, i.e. could have been predicted in early infancy without any laboratory tests. Although these risk factors were also significantly associated with the manifestation of allergic airway disease, the positive predictive value for this outcome at age 5 years was not yet as high, i.e. 50%.ConclusionInfants with very early signs of atopic dermatitis and a positive family history are candidates for early intervention measures against respiratory allergies.
Genetic and environmental factors affecting the allergenicity of birch (Betula pubescens ssp. czerepanovii [Orl.] Hämet‐Ahti) pollen
Authors: Ahlholm  , Helander  , Savolainen  
Published: March 2003

BackgroundEnvironmental variation, such as an increase of mean temperature due to the greenhouse effect, as well as the genetic factors may affect the allergenicity of pollen and thus, the prevalence of allergies. The connection between these factors and the allergen content of pollen is poorly understood.ObjectivesTo evaluate the role of environmental and genetic factors on the allergenicity of birch pollen.MethodsMountain birch (Betula pubescens ssp. czerepanovii (Orl.) Hämet‐Ahti) pollen was studied using SDS‐PAGE and IgE‐immunoblotting. Pollen samples were collected from the trees of 10 half‐sib families. The study trees from each family were reared in two tree line gardens where the daily mean temperatures were different during the growing season.ResultsThe quantitative analysis of band intensities suggested that the responses of the major birch pollen allergen, Bet v 1, were stronger in the samples collected from the garden with higher daily mean temperature. Half‐sib families and individual trees differed in their Bet v 1 content.ConclusionsOur results show that both genetic and environmental factors have an effect on the amount of Bet v 1. This suggests that breeding for trees low in allergen content may be possible.
Bee sting allergy in beekeepers
Authors: Eich‐Wanger  , MÜller  
Published: March 2003

BackgroundBeekeepers are strongly exposed to honey bee stings and therefore at an increased risk to develop IgE‐mediated allergy to bee venom.ObjectiveWe wondered whether bee venom‐allergic beekeepers were different from normally exposed bee venom‐allergic patients with regard to clinical and immunological parameters as well as their response to venom immunotherapy.MethodAmong the 459 bee venom‐allergic patients seen over the 5 year period 1987–91, 62 (14%) were beekeepers and 44 (10%) family members of beekeepers. These two groups were compared with 101 normally exposed bee venom‐allergic patients matched with the allergic beekeepers for age and sex, regarding clinical parameters, skin sensitivity, specific IgE and IgG antibodies to bee venom as well as safety and efficacy of venom immunotherapy.ResultsAs expected, allergic beekeepers had been stung most frequently before the first allergic reaction. The three groups showed a similar severity of allergic symptoms following bee stings and had an equal incidence of atopic diseases. Allergic beekeepers showed higher levels of bee venom‐specific serum IgG, lower skin sensitivity and lower levels of bee venom specific serum IgE than bee venom‐allergic control patients. A negative correlation between number of stings and skin sensitivity as well as specific IgE was found in allergic beekeepers and their family members, while the number of stings was positively correlated with specific IgG in these two groups. Venom immunotherapy was equally effective in the three groups, but better tolerated by allergic beekeepers than the two other groups. The majority of allergic beekeepers continued bee‐keeping successfully under the protection of venom immunotherapy.ConclusionThe lower level of sensitivity in diagnostic tests and the better tolerance of immunotherapy in allergic beekeepers is most likely related to the high level of specific IgG in this group.
Measles infection, measles vaccination and the effect of birth order in the aetiology of hay fever
Authors: Lewis  , Britton  
Published: March 2003

BackgroundIt has recently been suggested that measles infection may reduce the risk of atopy.ObjectiveTo study the independent effect of measles infection and measles vaccination on the occurrence of hay fever in a British national birth cohort.MethodsIn over 6000 children born in 1970, details of immunizations and childhood diseases were collected by parental interviews at ages 5, 10 and 16 years, and hay fever within the past year at age 16 years.ResultsIn univariate analysis, hay fever was less common in those contracting measles infection than in those not infected (OR 0.86, 95% CI 0.76–0.96), and more common in those given measles vaccination than in those not vaccinated (OR 1.16, 95% CI 1.03–1.31). However, these effects were strongly confounded by birth order, which was closely associated with the likelihood of receiving measles vaccination and with the risk of hay fever. A strong interaction between the effects of measles vaccination and infection, and birth order was found, such that in those with many older sibling contacts, hay fever was significantly and independently reduced in relation to both measles infection and measles vaccination relative to those who were neither infected nor vaccinated.ConclusionsBoth measles infection and measles vaccination in childhood appear to reduce the risk of hay fever in children with multiple older sibling contacts. Differential exposure or response to the measles virus may explain the effect of birth order on the occurrence of allergic disease.
Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients
Authors: Gruber  , Eber  , Mileder  , Modl  , Weinhandl  , Zach  
Published: March 2003

Background and objectiveAllergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non‐pharmacological challenges, has not been evaluated.MethodsTwenty‐six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non‐pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT.ResultsAfter 24 months, the SIT group showed a statistically significant reduction of the mean CACh‐induced changes of both forced expiratory volume in one second (−21.8 ± 2.7% vs −13.7 ± 2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (−48.9 ± 4.9% vs −27.9 ± 6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs 1/12; P < 0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness.ConclusionThese results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM‐allergic paediatric asthma patients.
A role for the hepatobiliary system in IgE‐mediated intestinal inflammation in the rat
Authors: Collins  , Leach  , Payne A. Mitchell  , Dai  , Jackson  
Published: March 2003

BackgroundFor many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra‐intestinal populations of mast cells may also contribute to IgE‐mediated intestinal damage.ObjectivesTo characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE‐mediated reactivity to dietary antigen.MethodsWistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP‐HSA. Additional animals were sensitized, then bile duct‐cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFα.ResultsHepatic mast cells display a mucosal mast cell‐like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P < 0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post‐antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P < 0.01). TNFα was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained.ConclusionThe data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE‐mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.