bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allergen‐specific immunotherapy with a monophosphoryl lipid A‐adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy‐induced blocking antibodies
Authors: Mothes N. , Heinzkill M. , Drachenberg K. J. , Sperr W. R. , Krauth M. T. , Majlesi Y. , Semper H. , Valent P. , Niederberger V. , Kraft D. , Valenta R. 
Published: September 2003

SummaryBackground
Allergen‐specific immunotherapy represents a causal form of treatment for IgE‐mediated allergies. The allergen extract‐based analyses of immunotherapy‐induced effects yielded highly controversial results regarding a beneficial role of therapy‐induced IgG antibodies.Objective
We analysed allergen‐specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1‐inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5).Results
The strong induction of allergen‐specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy‐induced allergen‐specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen‐dependent basophil histamine release was only obtained with sera containing therapy‐induced allergen‐specific IgG, but not with sera obtained before therapy or from placebo‐treated patients. Moreover, patients with therapy‐induced allergen‐specific IgG antibodies showed a reduced induction of allergen‐specific IgE responses during seasonal grass pollen exposure.Conclusion
Successful immunotherapy with the MPL‐adjuvanted grass pollen allergy vaccine is associated with the production of allergen‐specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate‐type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.
Residential characteristics predict changes in Der p 1, Fel d 1 and ergosterol but not fungi over time
Authors: Matheson M. C. , Dharmage S. C. , Forbes A. B. , Raven J. M. , Woods R. K. , Thien F. C. K. , Guest D. I. , Rolland J. M. , Haydn Walters E. , Abramson M. J. 
Published: September 2003

SummaryBackground
Allergen and fungal exposures are important risk factors for asthma. We conducted a longitudinal analysis of allergen levels in Melbourne homes between 1996 and 1998 to examine the effects of changing residential characteristics on allergen and fungal levels. We also examined the changes in levels of indoor allergens.Methods
The subjects were participants in the European Community Respiratory Health Survey (ECRHS) in Melbourne. In 1996, 485 subjects participated in a follow‐up study, which involved both home and laboratory visits. Dust and air samples were collected from participants' bedrooms and a validated residential questionnaire was administered. In 1998, 360 participants underwent further follow‐up. House dust mite (Der p 1) and cat allergens (Fel d 1) and ergosterol were measured in dust.Results
We observed moderate within home correlations between 1996 and 1998 in floor Der p 1 (intraclass correlation ICC=0.48), bed Der p 1 (ICC=0.61), Fel d 1 (κ=0.53) and ergosterol (ICC=0.28) levels. We found that the floor Der p 1 levels decreased from 1996 to 1998 in the homes of participants who moved to an attached home, moved their bedrooms to the first floor, removed fitted carpet or central heating. Replacing or vacuuming the mattress more than twice per year reduced levels of Der p 1 in the bed. Ergosterol levels were reduced by removing visible mould and fitted carpet.Conclusions
These findings provide evidence to support current advice with regard to allergen avoidance in patients with dust mite and fungal allergies.
Impaired secretion of interleukin‐4 and interleukin‐13 by allergen‐specific T cells correlates with defective nuclear expression of NF‐AT2 and jun B: relevance to immunotherapy
Authors: Faith A. , Richards D. F. , Verhoef A. , Lamb J. R. , Lee T. H. , Hawrylowicz C. M. 
Published: September 2003

SummaryBackground
Allergen immunotherapy (IT) is a successful treatment associated with decreased Th2 cytokine production by allergen‐specific T cells. We have previously demonstrated (Faith et al., J Immunol 1997; 159:53–57) that inhibition of Th2 cytokine production in vitro correlates with impaired tyrosine kinase activity through the TCR. The transcription factor complex, nuclear factor of activated T cells (NF‐AT), which regulates Th2 cytokine production is controlled by the activity of tyrosine kinases.Objective
To address whether decreased Th2 cytokine production by allergen‐specific CD4+ T cells following IT is correlated with altered translocation and nuclear expression of the NF‐AT family member, NF‐AT2, and the activator protein 1 (AP1) component of NF‐AT, jun B.Methods
T cell lines specific for insect venom phospholipase A2 (PLA) were derived from patients prior to and during conventional venom IT. Nuclear expressions of NF‐AT and jun B were assessed following stimulation through the TCR. Th1 and Th2 cytokine and IL‐10 production by insect venom‐specific T cells were also determined. Results were compared with a well‐established model system in which anergy was induced in cloned, allergen‐specific Th2 cells.Results
Impaired translocation and decreased expression of NF‐AT2 and jun B were detected in PLA‐specific T cell lines derived from bee venom‐allergic individuals following 16 weeks treatment compared to pre‐treatment. These results correlated with significantly reduced production of IL‐4 and IL‐13 and significantly increased production of IFN‐γ and IL‐10 by PLA‐specific T cells. Impaired IL‐4 and IL‐13 production also correlated with defective nuclear expression of NF‐AT2/jun B in cloned, anergic allergen‐specific Th2 cells.Conclusion
These results suggested that optimal production of IL‐4 and IL‐13 by allergen‐specific T cells is dependent on the nuclear expression of NF‐AT2 and jun B. Thus, specific inhibition of NF‐AT2/jun B might be an option in novel and improved forms of allergen IT.
Non‐bronchoscopic sampling and culture of bronchial epithelial cells in children
Authors: Doherty G. M. , Christie S. N. , Skibinski G. , Puddicombe S. M. , Warke T. J. , De Courcey F. , Cross A. L. , Lyons J. D. M. , Ennis M. , Shields M. D. , Heaney L. G. 
Published: September 2003

AbstractBackground
The bronchial epithelium is likely to play a vital role in airway diseases in children, such as asthma and viral‐associated wheeze. In adults, studies with primary bronchial epithelial cells cultured from samples obtained by fibre‐optic bronchoscopy have provided key insights into the role of the epithelial cell. However, it is difficult to justify bronchoscopy in children to obtain epithelial cells for research purposes.Objective
To examine the possibility of retrieving and culturing viable epithelial cells using a blind non‐bronchoscopic method from children undergoing elective surgery.Methods
Subjects were children undergoing elective surgery under general anaesthesia. Following intubation, non‐bronchoscopic bronchoalveolar lavage and non‐bronchoscopic bronchial brushing were performed. A sheathed bronchial cytology brush was advanced through the endotracheal tube, wedged and then withdrawn 2–3 cm before gentle sampling was used to collect bronchial epithelial cells. Initial samples were used to characterize the number, type and viability of epithelial cells recovered compared to a control group of adults undergoing standard bronchoscopic sampling. Subsequent samples were used to establish primary bronchial epithelial cell cultures in children both with and without wheezing illness.Results
A total of 63 children underwent bronchial brushing [38 male; median age 7.1 years (1.0–14.2 years]. Initial samples (n=30) showed recovery of viable epithelial cells comparable to that from a single brush obtained via a bronchoscope in an adult control group (n=11). In 27 (82%) of the subsequent 33 samples obtained non‐bronchoscopically from children, primary bronchial epithelial cell cultures were successfully established. There were no adverse effects attributable to sampling.Conclusion
We have shown that non‐bronchoscopic bronchial brushing is a safe and effective technique for recovering viable bronchial epithelial cells that consistently yield primary cultures. This method will facilitate examination of the role of the epithelium in paediatric disease.
Assessment of ocular and nasal irritation in asthmatics resulting from fragrance exposure
Authors: Opiekun R. E. , Smeets M. , Sulewski M. , Rogers R. , Prasad N. , Vedula U. , Dalton P. 
Published: September 2003

SummaryBackground
Many asthmatics report worsening of symptoms following exposure to odours and sensory irritants commonly found in household and cosmetic products. Despite this, little evidence exists to confirm the degree to which such subjective reports are correlated with localized, objective changes in the upper or lower airways following a fragranced product exposure.Objective
Subjective symptom reports were compared to objective measures in mild asthmatics, moderate asthmatics and non‐asthmatics following exposure to one of two fragranced household aerosol mixtures and a clean air control condition to determine if asthmatics reported greater subjective symptoms of nasal congestion or exhibited objective measures of elevated ocular irritation and nasal congestion following exposure than did healthy controls.Methods
Measures of nasal mucosal swelling, using acoustic rhinometry, and photographic assessments of ocular hyperemia, using macro‐photography, were taken before exposure, immediately after an initial 5‐min exposure and again following a 30‐min exposure to either of two, fragranced aerosol products and a clean air control. Self‐reports of nasal patency at each time‐point were also obtained.Results
Although moderate asthmatics tended to report more nasal congestion following fragranced product exposure than did non‐asthmatics, no exposure‐related changes in ocular redness or nasal mucosal swelling were observed among the three groups. Spirometry readings also failed to show evidence of any exposure‐related changes in pulmonary function.Conclusion
Despite claims that exposure to fragranced products may trigger ocular and respiratory symptoms among asthmatics, we found no evidence that 30 min of exposure to one of two fragranced aerosols elicited objective adverse effects in the ocular or nasal mucosa of mild and moderate asthmatics. While physiological mechanisms of fragrance impact may yet be responsible for some of the adverse reports among asthmatics following fragrance exposure, such reports may also reflect a non‐physiological locus of symptom perception triggered by other sensory cues.
Measurement of basophil‐activating capacity of grass pollen allergens, allergoids and hypoallergenic recombinant derivatives by flow cytometry using anti‐CD203c
Authors: Kahlert H. , Cromwell O. , Fiebig H. 
Published: September 2003

SummaryBackground
The assessment of the basophil‐activating potential is an important aspect in the development of improved preparations for specific immunotherapy. The aim of the study was to evaluate the suitability of CD203c expression as a measure of basophil activation to compare allergoids with original allergen extracts, and recombinant hypoallergenic allergen derivatives with recombinant wild‐type and natural allergens.Methods
Heparinized whole blood samples from grass pollen allergic subjects were stimulated with grass pollen allergens and allergen derivatives followed by labelling of the basophils with PE‐conjugated anti‐CD203c. After lysis of the erythrocytes and fixation, the basophils were detected by flow cytometry. In some experiments, histamine release was determined simultaneously.Results
Grass pollen allergoids revealed a 10–10 000‐fold reduction of basophil‐activating capacity measured by CD203c expression. The deletion mutant DM4 of rPhl p 5b showed stronger hypoallergenic characteristics in a range of 50–10 000‐fold reduction, whereas a combination mutant of rPhl p 5b and Phl p 6 revealed less hypoallergenic features. Histamine release experiments led to a similar outcome as CD203c measurement.Conclusions
The measurement of CD203c expression on basophils by flow cytometry provides a rapid and sensitive method for the estimation of the allergic or hypoallergenic features of allergen preparations. The results demonstrated the hypoallergenicity of grass pollen allergoids and of the rPhl p 5b variant DM4, which may be a candidate in future preparations for specific immunotherapy.
CD28/CTLA4 double deficient mice demonstrate crucial role for B7 co‐stimulation in the induction of allergic lower airways disease
Authors: Deurloo D. T. , Van Berkel M. A. T. , Van Esch B. C. A. M. , Hofhuis F. , Nijkamp F. P. , Oosterwegel M. A. , Van Oosterhout A. J. M. 
Published: September 2003

SummaryBackground
The existence of a third B7‐1/B7‐2 receptor was postulated in a recent study using a novel mouse strain lacking both CD28 and CTLA4 (CD28/CTLA4−/−).Objective
In the present study, it was investigated if T cell co‐stimulation via the putative B7‐1/B7‐2 receptor plays a role in the induction of Th2‐mediated asthma manifestations in mice.Methods
BALB/c wild‐type, CD28/CTLA4−/− and B7‐1/B7‐2−/− mice were sensitized and aerosol challenged with ovalbumin (OVA).Results
At 24 h after the last aerosol, wild‐type mice showed airway hyper‐responsiveness in vivo and up‐regulated levels of serum OVA‐specific IgE compared with the situation shortly before OVA challenge. In addition, eosinophil numbers and IL‐5 levels in the broncho‐alveolar lavage fluid and Th2 cytokine production by lung cells upon OVA re‐stimulation in vitro were observed. In agreement with an earlier study, we failed to induce any of the asthma manifestations in B7‐1/B7‐2−/− mice. Importantly, also CD28/CTLA4−/− mice showed no asthma manifestations upon OVA sensitization and challenge.Conclusion
These data clearly demonstrate that T cell co‐stimulation via the putative B7‐1/B7‐2 receptor appears to have no role in the induction of Th2‐mediated asthma manifestations in this murine model and, conversely, that CD28 signalling is crucial.
Immunological analysis of allergenic cross‐reactivity between peanut and tree nuts
Authors: De Leon M. P. , Glaspole I. N. , Drew A. C. , Rolland J. M. , O'Hehir R. E. , Suphioglu C. 
Published: September 2003

SummaryBackground
Peanut and tree nut allergy is characterized by a high frequency of life‐threatening anaphylactic reactions and typically lifelong persistence. Peanut allergy is more common than tree nut allergy, but many subjects develop hypersensitivity to both peanuts and tree nuts. Whether this is due to the presence of cross‐reactive allergens remains unknown.Objective
The aim of this study was to investigate the presence of allergenic cross‐reactivity between peanut and tree nuts.Methods
Western blotting and ELISA were performed using sera from subjects with or without peanut and tree nut allergy to assess immunoglobulin E (IgE) reactivity to peanut and tree nut extracts. Inhibition ELISA studies were conducted to assess the presence of allergenic cross‐reactivity between peanut and tree nuts.Results
Western blot and ELISA results showed IgE reactivity to peanut, almond, Brazil nut, hazelnut and cashew nut for peanut‐ and tree nut‐allergic subject sera. Raw and roasted peanut and tree nut extracts showed similar IgE reactivities. Inhibition ELISA showed that pre‐incubation of sera with almond, Brazil nut or hazelnut extracts resulted in a decrease in IgE binding to peanut extract, indicating allergenic cross‐reactivity. Pre‐incubation of sera with cashew nut extract did not cause any inhibition.Conclusion
These results show that multiple peanut and tree nut sensitivities observed in allergic subjects may be due to cross‐reactive B cell epitopes present in different peanut and tree nut allergens. The plant taxonomic classification of peanut and tree nuts does not appear to predict allergenic cross‐reactivity.
Assessment of T lymphocyte cytokine production in induced sputum from asthmatics: a flow cytometry study
Authors: Boniface S. , Koscher V. , Mamessier E. , El Biaze M. , Dupuy P. , Lorec A.‐M. , Guillot C. , Badier M. , Bongrand P. , Vervloet D. , Magnan A. 
Published: September 2003

SummaryBackground
Asthma results from a bronchial inflammation in which Th2 lymphocytes play a pivotal role, as shown in invasive bronchial biopsies and broncho‐alveolar lavages. Induced sputum (IS) is a non‐invasive method of recovery of bronchial cells, which can be repeated in the same patients. However, lymphocyte activation has not been studied in IS to date, because of the low number of T cells recovered. Herein we took advantage of flow cytometry, a method suitable for the study of small cell populations, to assess T cell cytokine production in IS.Objectives
(1) To assess induced sputum T cell cytokine production by flow cytometry in asthmatic subjects and controls. (2) To compare the T cell cytokine production between symptomatic and non‐symptomatic asthmatics.Methods
Thirteen asthmatics and 19 controls were included. Sputum was induced by a hypertonic saline. Sputum cells were stimulated and intracellular IL‐13 and IFN‐γ were detected in T cells by flow cytometry.Results
Stimulation induced an increase of IL‐13 and IFN‐γ production by T cells. This increase was higher in asthmatics. IL‐13‐producing T cells were increased in asthmatics after stimulation. In symptomatic asthma, IFN‐γ‐producing T cells were in higher proportion than in controlled asthma.Conclusion
IS T cell cytokine production indicates a basic Th2 bias in asthma, accompanied during symptoms by a Th1‐like activation. These results open the field for longitudinal studies of the variation of T cell activation in asthma.
Direct and indirect exposure to pets – risk of sensitization and asthma at 4 years in a birth cohort
Authors: Almqvist C. , Egmar A.‐C. , Hedlin G. , Lundqvist M. , Nordvall S. L. , Pershagen G. , Svartengren M. , Hage‐Hamsten M. van , Wickman M. 
Published: September 2003

SummaryIntroduction
There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results.Objective
To elucidate how early exposure to cat and dog relates to IgE‐sensitization and asthma in children at 2 and 4 years of age, in a prospective birth‐cohort study.Methods
Four thousand and eighty‐nine families with children born 1994–1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen‐specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders.Results
A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03–2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79–1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15–0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37–1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24–1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56–1.38).Conclusion
Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.
Histamine‐releasing factors, a heterogeneous group of different activities
Authors: Budde I. Kleine , Aalberse R. C. 
Published: September 2003

SummaryHistamine‐releasing factor or HRF is a collective term used for a heterogeneous group of factors with different modes of action. The current review is focussed on IgE‐dependent HRF that require the presence of certain types of IgE (designated IgE+) to induce histamine release. IgE+ might be a structurally different IgE molecule, or, alternatively, autoreactive IgE. A subgroup of IgE‐dependent HRF does not bind to IgE, such as cloned HRF p23. This factor turned out to be a basophil‐priming cytokine. Alternatively IgE‐dependent HRF might be an autoallergen. Several groups demonstrated IgE antibodies to human proteins. However, not all IgE autoallergen‐containing extracts induce histamine release of appropriately sensitized basophils. In culture supernatants of human mononuclear cells an autoallergenic activity (Agmn) is found, but no binding to IgE+ was found yet. Agmn might be an autoallergen, since it is cross‐reactive with a grass pollen allergen in the stripped basophil assay.IgE‐dependent HRF and IgE+ may play a role in the late allergic reaction (LAR). However, IgE+ responsiveness to Agmn (IgEmn+) was not required for a bronchial LAR. IgEmn+ is associated with chronic allergic disease, since the prevalence of IgEmn+ is high in the serum of severe asthmatics and atopic dermatitis patients. Our hypothesis is that exogenous allergens induce IgE antibodies cross‐reactive with an endogenous protein. During a LAR, these endogenous proteins are released and the subsequent IgE‐mediated reaction prolongs and aggravates the allergic and/or asthmatic symptoms.In conclusion, HRF is a confusing term since it is used for different activities. It might be better to avoid this terminology on and just describe the activity of the factors. Autoallergenic activity is likely to explain most, if not all, IgE‐dependent activity.