bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discontinuous IgE‐binding epitopes contain multiple continuous epitope regions: results of an epitope mapping on recombinant Hol l 5, a major allergen from velvet grass pollen
Authors: Schramm G. , Bufe A. , Petersen A. , Haas H. , Merget R. , Schlaak M. , Becker W.‐M. 
Published: March 2003

The knowledge of IgE‐binding epitopes on allergen molecules is important for better understanding allergen–antibody interactions and, thus, for developing new strategies for immunotherapy.Our purpose was to more precisely define the number and structure of IgE‐binding epitopes of a paradigmatic major grass pollen allergen.We performed an IgE‐binding epitope mapping of rHol l 5, a group V pollen allergen of velvet grass (Holcus lanatus), with overlapping fragments (length between 15 and 186 amino acids), which were expressed in E. coli as MBP fusion proteins. Using sera of 65 grass pollen allergic patients, the fragments were analysed by immunoblotting for IgE reactivity. Specificity of antibody binding was confirmed by competitive blot inhibition assays.At least four different continuous IgE‐binding epitopes were identified on small fragments (about 30 amino acids), and at least five different discontinuous IgE‐binding epitopes on larger fragments, which were destroyed by further fragmentation. The fragments were differentially recognized by individual patients' sera. By investigating IgE‐binding to one of the small fragments in more detail, we found further epitope regions on this fragment. It was noteworthy that IgE reactivity to small fragments was weak compared to large fragments or to the complete molecule. Competitive blot inhibition experiments showed that binding of IgE antibodies to the small fragments was specific but with lower avidity than to the complete rHol l 5.rHol l 5 harbours multiple discontinuous as well as continuous IgE‐binding epitopes spread over the whole molecule, which were individually recognized by IgE antibodies from different patients. Low avidity of IgE antibodies to small fragments suggests that the continuous epitope regions do not represent the complete epitope and are most probably parts of discontinuous epitopes.
Inhibition of IgE‐induced activation of human mast cells by IL‐10
Authors: Royer B. , Varadaradjalou S. , Saas P. , Guillosson J. J. , Kantelip J. P. , Arock M. 
Published: March 2003

Background IL‐10 exhibits anti‐inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen‐induced airway inflammation in vivo in murine models. The effects of IL‐10 on the allergic activation of human MC are presently unknown.Objective In light of the well‐known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL‐10. Moreover, the impact of IL‐10 on MC‐derived proinflammatory mediators is still unknown. Thus, the objective of this study was to investigate the effects of IL‐10 on the release of inflammatory mediators by IgE/anti‐IgE‐challenged human cord blood‐derived mast cells (CBMC), used as an in vitro model of MC phenotypically similar to human lung MC.Materials and methods Highly purified human MC were obtained by a first step of long‐term culture of cord blood mononuclear cells in the presence of human recombinant stem cell factor (rhSCF) and of human recombinant IL‐6 (rhIL‐6), followed by a second step of purification by depletion of contaminating cells with an immunomagnetic method. The cells were treated with human IgE, then challenged with anti‐human IgE, in the presence or the absence of recombinant rhIL‐10 used at various concentrations. Histamine, tumour necrosis factor‐alpha (TNF‐α), IL‐5 and IL‐8 were measured in the various supernatants collected at different times after the beginning of the challenge.Results IL‐10 inhibited the release of TNF‐α and of IL‐8, but not of IL‐5, by activated CBMC. Interestingly, IL‐10 also inhibited the release of histamine by activated CBMC, contrasting with data reported for rodent MC.Conclusions These findings suggest that IL‐10 might have anti‐inflammatory effects on IgE/anti‐IgE‐challenged human MC by inhibiting their release of TNF‐α, IL‐8 and histamine. These data provide new insights into the control of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.
Comparison of once daily fluticasone propionate aqueous nasal spray with once daily budesonide reservoir powder device in patients with perennial rhinitis
Authors: Kivisaari E. , Baker R. C. , Price M. J. 
Published: March 2003

Background Previous studies comparing the corticosteroids fluticasone propionate (FP) and budesonide (BUD) in both perennial and seasonal rhinitis have shown no consistent difference between treatments. However, the therapeutic outcomes may have been influenced by study design.Objective To compare the effect of FP aqueous nasal spray (ANS; 200 µg/day) with BUD reservoir powder device (RPD; 200 µg/day) on rhinitis symptoms, productivity loss and device preference in patients with perennial rhinitis.Methods After a 2‐week run‐in period, 440 patients were randomized to receive either FPANS, BUD RPD or matched placebo (ANS or RPD) for 8 weeks, followed by an open‐label 4‐week follow‐up treatment with FPANS. Patients completed diary card visual analogue scores for nasal symptoms, and questionnaires on satisfaction with the treatment and preferred choice of device.Results During weeks 1–4, the visual analogue total nasal symptom scores (VATNS) in the FPANS group were significantly lower than scores in the BUD RPD group (mean difference =−17.8; 95% CI = −34.4, −1.3; P = 0.036). FPANS also significantly reduced the VATNS compared with the ANS placebo at all time‐points assessed (P ≤ 0.005). BUD RPD did not significantly differ from the RPD placebo at weeks 5–8 (P = 0.167), or the ANS placebo at any time‐point (P ≤ 0.151). Over the 8‐week treatment period FPANS was significantly more effective than BUD RPD at reducing sneezing (mean difference =−4.4; 95% CI = −8.6, −0.3; P = 0.036) and nasal itching (mean difference =−5.3; 95% CI = −9.9, −0.8; P = 0.022), and was significantly superior to the ANS placebo for all symptoms assessed at weeks 1–4 and 1–8 (P < 0.016). At the same time‐points BUD RPD was no better at alleviating nasal itching than the RPD placebo (P ≤ 0.306), and compared with the ANS placebo, significantly reduced only one symptom; nasal blockage (P ≤ 0.016). After 8 weeks of treatment, patients preferred the ANS device to the RPD (P < 0.001), and at 12 weeks a significantly greater number of patients were satisfied with FPANS treatment compared with BUD RPD (P = 0.0019) or the respective placebos (P = 0.0001).Conclusion FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo‐controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.
Novel B and T cell epitopes of chicken ovomucoid (Gal d 1) induce T cell secretion of IL‐6, IL‐13, and IFN‐γ
Authors: Holen E. , Bolann B. , Elsayed S. 
Published: March 2003

Background Chicken ovomucoid (OM, Gal d 1) has an important role in the pathogenesis of IgE‐mediated allergic reactions to hen's egg white.Objectives The purpose of this study was to clarify the mechanisms of T cell recognition of ovomucoid using intact OM and chemically modified, characterized and homogeneous solid phase synthetic peptides covering the whole molecule.Methods Eighteen overlapping peptides were prepared by solid phase F‐moc polyamide peptide synthesis (SPPS), characterized and high‐pressure liquid chromatography (HPLC) purified. The peptides, together with intact, denatured and oxidized OM, were used to stimulate patient‐derived cell cultures for mapping T cell epitopes. Proliferation responses, T cell phenotype and cytokine secretion using peripheral blood mononuclear cells (PBMC) from eight individuals and T cell lines (TCL) derived from six hen's egg‐allergic patients, were examined. In addition, intact, denatured, oxidized and deglycosylated OM, as well as the peptides solely or with their keyhole limpet haemocyanin (KLH) complexes, were tested. For locating IgE and IgG B cell epitopes, seven egg‐allergic patient sera and three OM‐polyclonal sera were used. Healthy non‐allergic individuals were included as controls.Results Seven peptides were recognized by specific IgE, while OM‐specific TCL recognized 10 peptides. Six of the OM peptides were commonly recognized both by patient S‐IgE and blood‐derived TCL. Among those, one novel epitope, peptide OM 61–74, had the ability to bind IgE. Another peptide, OM 101–114, was recognized by IgE and IgG sera, but not by any of the TCLs. In contrast, the peptides OM 41–56, OM 71–84, OM 131–144 and OM 171–186 were exclusively T cell epitopes with no affinity to specific antibodies. Abundant TCL secretion of IFN‐γ, IL‐6, IL‐4, IL‐13, IL‐10 and TNF‐α in response to OM stimulation indicates the contribution of Th2 as well as Th1/Th0 CD4+ cell subsets. For allergic patients moderate amounts of IFN‐γ, IL‐13, and high amounts of IL‐6, were secreted in response to TCL stimulation by OM peptides. High amounts of IL‐6 were secreted in response to all molecular forms of OM (intact‐, modified‐OM and the peptides 71–84 and 51–64) when TCLs from two non‐allergic donors were used.Conclusions One novel B cell epitope (OM 61–74) and 10 T cell epitopes have been identified. The most reactive epitopes of the OM molecule comprise the motifs 1–14 to 71–84, the overlapping peptide‐pairs OM 121–134 and OM 131–144 and peptides OM 161–174 and 171–186. Peptides OM 1–14 and 171–186 are the only ones capable of inducing IL‐4 secretion. Only one peptide (OM 11–24) induces IL‐10 secretion. Those peptides recognized as both T and B cell epitopes or only T cell epitopes, have the potential to induce T cell secretion of moderate to high amounts of IL‐13, IFN‐γ and particularly IL‐6.
Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests
Authors: Hill D. J. , Hosking C. S. , Reyes‐Benito L. V. 
Published: March 2003

Background Double‐blind placebo‐controlled food challenges (DBPCFC), the gold standard for the diagnosis of food hypersensitivity, are time‐consuming and not without risk. We have recently reported skin prick test (SPT) weal diameters to cow's milk, egg and peanut above which infants and young children referred for investigation of suspected food allergy showed an adverse reaction on food challenge. We have termed these the ‘100% diagnostic SPT levels’. In this study, we compare in vivo with in vitro measurement of IgE antibody levels to three common food allergens — cow's milk, egg and peanut — in infants and young children with suspected food allergy, in order to reduce the need for food challenges.Methods SPT and Enzyme Allergo‐sorbent Test (EAST) (from 1992 to 1998) and CAP values (from 1999 to 2000) were performed in 820 children < 2 years of age with suspected allergy to cow's milk and/or egg and/or peanut. SPT levels previously shown to be diagnostic of challenge‐proven allergy to cow's milk, egg and peanut were used as the ‘100% diagnostic SPT levels’ and compared with EAST and CAP values associated with IgE food allergy according to the manufacturer's definition.Results McNemar's test showed a significant difference between the ‘100% diagnostic SPT levels’ and positive EAST in identifying patients who did not require food challenge for cow's milk (P = 0.01), egg (P < 10−6) and peanut (P < 10−6), and a significant difference between the ‘100% diagnostic SPT levels’ and positive CAP (P < 10−6) for egg and peanut but not cow's milk. Twenty‐three per cent of food challenges which, based on the results of EAST and CAP, would have been necessary to confirm the diagnosis of food allergy were avoided by the use of the ‘100% diagnostic SPT levels’.Conclusion The use of the ‘100% diagnostic SPT levels’ compared with in vitro measurement of IgE antibody to cow's milk, egg and peanut reduces the need for food challenge in young children with suspected food allergy.
Cetirizine inhibits skin reactions but not mediator release in immediate and developing late‐phase allergic cutaneous reactions. A double‐blind, placebo‐controlled study
Authors: Nielsen P. N. , Skov P. S. , Poulsen L. K. , Schmelz M. , Petersen L. J. 
Published: March 2003

Background Recent reports have indicated cetirizine, a potent H1‐receptor antagonist, to possess a number of anti‐inflammatory effects, e.g. inhibition of mast cell degranulation and inhibition of leucocyte migration and activation.Objective The aim of this study was to compare the effects of cetirizine on skin responses and mediator release in intact skin in immediate and developing late‐phase allergic reactions by microdialysis technique.Methods Cetirizine 10 mg once daily or matching placebo were administered to 10 atopic subjects for 6 days followed by a 2‐week washout in a randomized, double‐blind, placebo‐controlled, cross‐over trial. Immediate skin test responses to allergen, codeine, and histamine and late‐phase reactions to allergen were assessed. The time course of extracellular levels of inflammatory mediators in intact skin were monitored by microdialysis techniques using 2 kDa and 3 MDa cut‐off fibers, respectively.Results Cetirizine significantly reduced immediate weal and flare reactions to allergen, codeine, and histamine. Injection of allergen, but not buffer controls, induced a significant release of histamine, tryptase, prostaglandin D2, total protein, and eosinophilic cationic protein. No significant increase of leukotriene B4 and myeloperoxidase was observed. Cetirizine inhibited early total protein extravasation by 40%, but this did not reach a significant level. None of the inflammatory mediators were significantly inhibited by cetirizine. Cetirizine significantly reduced the late‐phase skin induration to allergen by approximately 30%.Conclusion Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetirizine to be a potent H1‐receptor antagonist with no effect on mast cell activation. It did not inhibit any of the late‐phase mediators, but it reduced the late skin reaction. These data suggest that mediators other than those actually measured may play a significant role in the clinical late‐phase reaction.
Prevalence of respiratory and atopic disorders in Chinese schoolchildren
Authors: Wong G. W. K. , Hui D. S. C. , Chan H. H. , Fok T. F. , Leung R. , Zhong N. S. , Chen Y. Z. , Lai C. K. W. 
Published: March 2003

Background Epidemiological surveys have shown that the prevalence of asthma in the Asian population is relatively low. Within the Chinese population, schoolchildren from Hong Kong were found to have the highest rate of asthma.Objective To compare the prevalence of respiratory and atopic disorders, and to assess the role of atopy in the development of asthma, in Chinese schoolchildren from Hong Kong, Beijing and Guangzhou.Methods Community‐based random samples of schoolchildren aged 9–11 years from three Chinese cities (Hong Kong, Beijing and Guangzhou) were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n = 10902), skin‐prick tests (n = 3479) and skin examination (n = 3479).Results The prevalence rates of current wheeze, speech limiting wheeze, rhinoconjunctivitis and flexural dermatitis were significantly more common in Hong Kong than in Beijing or Guangzhou. The atopy rate was also higher in Hong Kong (41.2%) than in Beijing (23.9%) or Guangzhou (30.8%). Atopy was strongly correlated with current wheeze (OR 7.74; 95% CI = 5.70–10.51). Subgroup analyses of children from Hong Kong revealed that children born in mainland China who had subsequently migrated to Hong Kong had a significantly lower rate of allergic symptoms and atopy than those children born in Hong Kong.Conclusion Using a standardized written questionnaire along with a skin prick test and skin examination, we confirmed that the prevalence of asthma, allergic diseases and atopy was highest in schoolchildren from Hong Kong. Atopic sensitization is an important factor associated with asthma in Chinese children.
Early introduction of cereals into children's diets as a risk‐factor for grass pollen asthma
Authors: Armentia A. , Bañuelos C. , Arranz M. L. , Del Villar V. , Martín‐Santos J.‐M. , Gil F. J. M. , Vega J. M. , Callejo A. , Paredes C. 
Published: March 2003

Background The prevalence of asthma has increased from the 1950s to the 1990s. The relationship between diet and asthma is an area of controversy that has never been fully evaluated. Attempts at dietary prevention of asthma have produced conflicting results. We have recently identified allergens from cereals that show cross‐reactivity with proteins in grass pollen. An early intake of cereals in the diet during early life might cause IgE sensitization to cereals. It is not known whether such sensitization predisposes the development of allergy to pollen.Methods To test this hypothesis, a cross‐sectional study and an observational case‐control analysis of reviewed data were carried out on 16381 patients who had been admitted to our Allergy Unit between 1989 and 1999. All the patients underwent allergy tests to identify asthma risk‐factors. All information in our data base was analysed using the SPSS computer system.Results There has been an increase of 7.8% in incidences of allergic asthma and a 7.3% increase in asthma due to grass pollen in the last decade. Grass‐pollen asthma was associated with sensitization to cereals. The early introduction of cereals in the diet of children was found to be a risk factor for grass‐pollen asthma (OR = 5.95; 95% CI 3.89–9.10).Conclusions These findings document the progression of allergic asthma during a decade in a large sample of people who were influenced by similar environmental conditions and studied with the same diagnostic methods. This study represents the largest database of patients in which a common food is shown to be a risk factor for asthma.
Atopic asthma: differential activation phenotypes among memory T helper cells
Authors: Lara‐Marquez M. L. , Moan M. J. , Cartwright S. , Listman J. , Israel E. , Perkins D. L. , Christiani D. C. , Finn P. W. 
Published: March 2003

Background T cells have been implicated in the pathogenesis of atopic asthma. We have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially activated relative to naïve T helper cells (CD4+CD45RA+) after bronchial allergen challenge. However, specific T helper subpopulations that are activated in atopy and/or asthma remain undefined.Objective To determine the T helper subpopulations and activation phenotypes relevant to acute and stable asthma that may be common with or distinct from atopy.Methods Two groups of atopic asthmatics (ten acute and nine stable asthmatics) and two non‐asthmatic groups (14 non‐asthmatic atopics and eight normal non‐atopic controls) were analysed. Ten acute asthmatics were assessed in the emergency room during an acute episode (FEV1 43.6% ± 18.4). Nine stable asthmatics were assessed during a symptom‐free period (FEV1 85% ± 6). Using multiple colour flow cytometry we analysed T cell subpopulations and the expression of IL‐2‐receptor (IL‐2R) and MHC‐class II antigens (MHC II) on naïve and memory T helper cells in the peripheral blood of asthmatic and non‐asthmatic groups.Results Atopic asthmatics (acute and stable) had an increased percentage of memory T helper cells expressing IL‐2R compared with normal non‐atopics (mean SD 16.1 ± 6%, 12.4 ± 2% and 7.7 ± 1.8%, P < 0.05) but not compared with non‐asthmatic atopics (10 ± 3.5%). Naïve T helper cells had low expression of IL‐2R and MHC II in all four groups. MHC II antigen expression was increased in memory T helper cells of asthmatics (acute and stable) compared with normal non‐atopics (13.9 ± 7.5, 10.6 ± 5 and 4.9 ± 2.5, P < 0.05) but not compared with non‐asthmatic atopics (7.92 4). A novel finding was that IL‐2R and the MHC II molecules were mainly expressed in non‐overlapping populations and coexpression was found predominantly on memory T helper cells. Asthmatics (acute and stable) had higher proportion of double positive memory T helper cells (IL‐2R+MHC II+) compared with both non‐asthmatic groups (P < 0.05).Conclusions We demonstrate a differential expression of IL‐2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non‐overlapping IL‐2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL‐2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non‐asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non‐asthmatics.
Effects of suplatast tosilate, a new type of anti‐allergic agent, on airway cough hypersensitivity induced by airway allergy in guinea‐pigs
Authors: Myou S. , Fujimura M. , Kurashima K. , Kita T. , Tachibana H. , Ishiura Y. , Abo M. , Nakao S. 
Published: March 2003

Background Cough receptor hypersensitivity is a fundamental feature of some conditions presenting with chronic non‐productive cough. Suplatast tosilate, an anti‐allergic agent, is a T helper (Th)2 cytokine inhibitor that inhibits the synthesis of interleukin (IL)‐4, IL‐5, immunoglobulin (Ig)E production, and local eosinophil accumulation.Objective The purpose of this study was to investigate the effect of suplatast on antigen‐induced airway cough hypersensitivity and eosinophil infiltration into the airway.Methods Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10−8, 10−6 and 10−4 M) was counted 24 h after an antigen challenge in conscious guinea‐pigs and then bronchoalveolar lavage was performed. We investigated the effect of single (before antigen challenge or capsaicin provocation) or repetitive treatment with intraperitoneal suplatast at a dose of 10 or 30 mg/kg on antigen‐induced cough hypersensitivity.Results Twenty‐four hours after antigen challenge, guinea‐pigs developed an increase in cough receptor sensitivity to inhaled capsaicin and eosinophil infiltration in the airways. After a 2‐week treatment with suplatast, but not after only a single treatment before antigen challenge or capsaicin provocation, the antigen‐induced early phase bronchoconstriction, cough hypersensitivity, and airway eosinophilia were inhibited in a dose‐dependent manner.Conclusion These results indicate that suplatast inhibits airway cough hypersensitivity underlying allergic eosinophilic inflammation.