bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infant feeding patterns affect the subsequent immunological features in cow's milk allergy
Authors: Saarinen  , Savilahti  
Published: March 2003

BackgroundThe first exposure to food antigens provokes an immune reaction in an infant, its type depending on the quantity and frequency of doses and the age at introduction, and also being influenced by genetic factors. Most infants develop tolerance to food antigens, but in a small minority they provoke adverse symptoms.ObjectiveTo study the effects of breast and formula feeding and other environmental and genetic factors on the subsequent type of cow's milk allergy classified by the presence or absence of immunoglobulin (Ig) E antibodies to cow's milk.MethodsA cohort of 6209 infants was followed prospectively from birth for symptoms of cow's milk allergy. The infant‐feeding regimen was recorded at the maternity hospital and at home. At a mean age of 6.7 months, a total of 118 infants (1.9%) reacted adversely to a challenge with cow's milk. Before the challenge, the response to a skin‐prick test with cow's milk and serum IgE cow's milk antibodies was measured.ResultsAt challenge, 75 (64%) infants showed IgE‐positive reactions to cow's milk, their most common symptom being acute‐onset urticaria. Significant risk factors for the presence of IgE cow's milk antibodies in allergic infants were long breast‐feeding (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.6–9.8), exposure to cow's milk at the maternity hospital (OR 3.5, 95% CI 1.2–10.1) and breast‐feeding during the first 2 months at home either exclusively (OR 5.1, 95% CI 1.6–16.4) or combined with infrequent exposure to small amounts of cow's milk (OR 5.7, 95% CI 1.5–21.6). Fifty infants had their first adverse symptoms during exclusive breast‐feeding, and 32 infants were sensitized during exclusive breast‐feeding. Most of the infants in both cases were IgE‐positive: 37 and 23, respectively.ConclusionsIn infants who are prone to developing cow's milk allergy, prolonged breast‐feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE‐mediated response to cow's milk.
HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in Taiwan
Authors: Hu  , Hsu  , Lin  , Hsieh  , Chua  
Published: March 2003

BackgroundHouse dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen‐specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM.ObjectiveThis study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus.MethodsTwo hundred and forty‐eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) ‐specific IgE and Der p 2‐specific IgG antibodies were detected by ELISA, while HLA class II ‐DRB1, ‐DQA1, ‐DQB1, ‐DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence‐specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen‐specific IgE and IgG antibodies were performed.ResultsThere was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM‐specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5‐specific IgE responsiveness. However, we found that HLA‐DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA‐DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P ≤ 0.0001, P ≤ 0.0007, Pc ≤ 0.010).ConclusionWe clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA‐DPB1*0201 involvement in protecting subjects from HDM‐specific IgE responsiveness awaits further investigation.
Effects of luteolin, quercetin and baicalein on immunoglobulin E‐mediated mediator release from human cultured mast cells
Authors: Kimata  , Shichijo  , Miura  , Serizawa  , Inagaki  , Nagai  
Published: March 2003

BackgroundFlavonoids have a variety of activities including anti‐allergic activities, and are known to inhibit histamine release from human basophils and murine mast cells.ObjectiveThe effects of luteolin, a flavone, on the immunoglobulin (Ig) E‐mediated allergic mediator release from human cultured mast cells (HCMCs) were investigated and compared with those of baicalein and quercetin.MethodsHCMCs were sensitized with IgE, and then treated with flavonoids before challenge with antihuman IgE. The amount of released mediators was determined as was mobilization of intracellular Ca2+ concentration, protein kinase C (PKC) translocation and phosphorylation of intracellular proteins were detected after anti‐IgE stimulation.ResultsLuteolin, baicalein and quercetin inhibited the release of histamine, leukotrienes (LTs), prostaglandin D2 (PGD2), and granulocyte macrophage‐colony stimulating factor (GM‐CSF) from HCMC in a concentration‐dependent manner. Additionally, the three flavonoids inhibited A23187‐induced histamine release. As concerns Ca2+ signalling, luteolin and quercetin inhibited Ca2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC activity strongly, although baicalein did slightly. The suppression of Ca2+ and PKC signallings might contribute to the inhibition of mediator release. The activation of extracellular signal‐regulated kinases (ERKs) and c‐Jun NH2‐terminal kinase (JNK), that were activated just before the release of LTs and PGD2 and GM‐CSF mRNA expression in IgE‐mediated signal transduction events, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen‐activated protein kinase (p38 MAPK) pathway.ConclusionThese results indicate that luteolin is a potent inhibitor of human mast cell activation through the inhibition of Ca2+ influx and PKC activation.
Airway eosinophilia is not a requirement for allergen‐induced airway hyperresponsiveness
Authors: Tournoy  , Kips  , Schou  , Pauwels  
Published: March 2003

BackgroundHouse dust mites (HDMs) are the major source of perennial allergens causing human allergic asthma. Animal models mimicking as closely as possible the allergic features observed in human asthma are therefore interesting tools for studying the immunological and pathophysiological mechanisms involved. Especially the role of eosinophils and allergen‐specific immunoglobulin (Ig) E in the pathophysiology of airway hyperresponsiveness (AHR) remains a subject of intense debate.ObjectiveTo develop a mouse model of allergic airway inflammation and hyperresponsiveness based on the use of purified house dust mite allergen (Der p 1) as clinical relevant allergen. Furthermore, we studied the effects of low dose allergen exposure on the airway eosinophilia and AHR.MethodsOn day 0, C57Bl/6 mice were immunized with purified Der p 1 intraperitoneally. From day 14–20, the mice were exposed daily to a 30‐min aerosol of different concentrations of house dust mite extract.ResultsMice, actively immunized with Der p 1 and subsequently exposed to HDM aerosols, developed AHR, eosinophil infiltration of the airways and allergen‐specific IgE. Moreover, lowering the concentration of the HDM aerosol also induced AHR and IgE without apparent eosinophil influx into the airways. Der p 1‐sensitized mice exposed to PBS produced IgE, but did not show AHR or eosinophil influx.ConclusionThis in vivo model of HDM‐induced allergic airway changes suggests that AHR is not related to either eosinophil influx or allergen‐specific serum IgE, thereby reducing the importance of these factors as essential elements for allergic AHR.
The 18‐kDa form of cat allergen Felis domesticus 1 (Fel d 1) is associated with gelatin‐ and fibronectin‐degrading activity
Authors: Ring  , Wan  , Schou  , Kroll Kristensen  , Roepstorff  , Robinson  
Published: March 2003

BackgroundFel d 1, an important allergen from domestic cats, is a significant cause of asthma. In addition to directly promoting IgE synthesis, other biological activities of allergens may contribute to either allergic sensitization or the magnitude of allergic effector responses. For example, allergens that degrade proteins have been suggested to facilitate allergen presentation by increasing parallelular permeability of airways epithelium. However, little information exists to indicate whether Fel d 1 has other activities relevant to allergic responses.ObjectiveTo study whether Fel d 1 is associated with enzyme activity.MethodsFel d 1 was obtained by a rigorous purification strategy and its identity confirmed by laser desorption mass spectrometry, cleavage and sequencing. The ability of Fel d 1 to degrade gelatin, fibronectin and the artificial substrate N‐benzoyl‐FVR‐p‐nitroanilide was studied. The effect of Fel d 1 on the morphology of tight junctions in epithelial cell monolayers was also investigated.ResultsThe 18‐kDa form of Fel d 1 caused degradation of denatured collagens (gelatin) and cleaved a 20‐kDa fragment from the A chain of plasma fibronectin. Catalytic activity was not altered by inhibitors of cysteine peptidases, matrix metallopeptidases or by removal of divalent cations. In contrast, aprotinin and TLCK were inhibitors of Fel d 1. The absence of a serine peptidase catalytic triad in Fel d 1, together with the stoichiometry of the inhibition of TLCK and aprotinin, suggest that their inhibitory action may be due to noncatalytic site interactions. Alternatively, highly purified Fel d 1 may be associated with an active contaminant, although none were found.ConclusionThese results suggest that Fel d 1 is another example of a domestic allergen which is associated with enzyme activity. It remains to be established whether the activity resides in Fel d 1 itself or in an unresolved, and possibly related, protein.
Suppression of neural activity of bronchial irritant receptors by surface‐active phospholipid in comparison with topical drugs commonly prescribed for asthma
Authors: Hills  , Chen  
Published: March 2003

BackgroundMuch indirect evidence has been put forward previously in support of the concept that surface‐active phospholipid (SAPL) normally masks irritant receptors in the lungs and upper respiratory tract; but this physical barrier is deficient in asthmatics, imparting hyperresponsiveness of the bronchoconstrictor reflex.ObjectiveTo determine whether exogenous SAPL applied to bronchial mucosa reduces the sensitivity of irritant receptors to a standard challenge used clinically to diagnose asthma and to compare the effects with those of corticosteroids and β‐stimulation.MethodsNerve fibres in the vagi were monitored to record action potentials from irritant receptors identified in the upper airways of rat lungs in response to a methacholine challenge. SAPL in the form of dipalmitoyl phosphatidylcholine (PC) and phosphatidylglycerol (PG) — 7 : 3 PC:PG — was applied as a fine dry powder to enhance surface activity and, hence, chemisorption to epithelium. Comparison was also made with clinical doses of i.v. hydrocortisone and instilled salbutamol together with liquid or solid controls, as appropriate.ResultsNeural activity of irritant receptors was found to be significantly (P = 0.0018) decreased by topical SAPL by 35.8% in response to a methacholine challenge in contrast to an increase of 11.2% in response to a solid (lactose) control. Instilled salbutamol and i.v. hydrocortisone also decreased responses to the same challenge by 43.4% and 14.7%, respectively, in contrast to a liquid (saline) control which increased by 24.5%.ConclusionsSurface‐active phospholipid has an appreciable effect upon irritant receptors in rat airways, reducing neural response to a methacholine challenge by an amount comparable to that of Salbutamol. These results support the concept of SAPL masking bronchial irritant receptors and warrant placebo‐controlled clinical trials of this dry powder as a means of controlling asthma without the side‐effects of current medication. Other possible roles discussed for the SAPL epithelial barrier include the exclusion of viruses and allergens.
Markers for early sensitization and inflammation in relation to clinical manifestations of atopic disease up to 2 years of age in 133 high‐risk children
Authors: Laan  , Baert  , Bijl  , Vredendaal  , De Waard‐Van Der Spek  , Oranje  , Savelkoul  , Neijens  
Published: March 2003

BackgroundThe combination of genetic susceptibility and environmental factors induce allergic sensitization and subsequently local inflammation, resulting in atopic manifestations.ObjectiveTo examine whether immunological features reflecting sensitization (total and specific IgE levels, allergen‐induced proliferative responses and skin tests) and markers of inflammation (plasma sE‐selectin and blood eosinophils) are related to the clinical expression of atopy and whether they precede atopic disease in children up to 2 years of age.MethodsThe development of these markers during the first 2 years of life was studied prospectively in 133 newborns at high risk to develop atopic disease.ResultsThe prevalence of atopic disease increased from 25% at 12 months to 32% at 24 months of age. The children with food allergy at 12 months, who all had atopic dermatitis (AD), turned out to have asthma‐like disease in 40% and AD in 100% at the age of 24 months. Total IgE levels increased with time and from 12 months onward levels started to differ markedly between atopics and nonatopics. Food‐specific IgE antibodies were significantly associated with AD (relative risk [RR] = 2.39), food (RR = 1.32) and upper‐airway allergy (RR = 1.20), and house dust mite‐specific IgE antibodies with upper‐airway allergy (RR = 5.00). A positive skin test was significantly associated with AD (RR = 2.90) and food allergy (RR = 1.36). The inflammation markers investigated, were not related to the clinical expression or preceded atopic disease at 2 years of age in high‐risk children.ConclusionPositive skin tests and specific IgE to food or inhalant allergens were related to the clinical expression of different atopic diseases. The combination of AD and food allergy at 12 months reflected the strongest risk factor in this high risk cohort for the development of asthma‐like disease at 24 months of age.
Lessons for management of anaphylaxis from a study of fatal reactions
Authors: Pumphrey  
Published: March 2003

BackgroundThe unpredictability of anaphylactic reactions and the need for immediate, often improvised treatment will make controlled trials impracticable; other means must therefore be used to determine optimal management.ObjectivesThis study aimed to investigate the circumstances leading to fatal anaphylaxis.MethodsA register was established including all fatal anaphylactic reactions in the UK since 1992 that could be traced from the certified cause of death. Data obtained from other sources suggested that deaths certified as due to anaphylaxis underestimate the true incidence. Details of the previous medical history, the reaction and necropsy were sought for all cases.ResultsApproximately half the 20 fatal reactions recorded each year in the UK were iatrogenic, and a quarter each due to food or insect venom. All fatal reactions thought to have been due to food caused difficulty breathing that in 86% led to respiratory arrest; shock was more common in iatrogenic and venom reactions. The median time to respiratory or cardiac arrest was 30 min for foods, 15 min for venom and 5 min for iatrogenic reactions. Twenty‐eight per cent of fatal cases were resuscitated but died 3 h–30 days later, mostly from hypoxic brain damage. Adrenaline (epinephrine) was used in treatment of 62% of fatal reactions but before arrest in only 14%.ConclusionsImmediate recognition of anaphylaxis, early use of adrenaline, inhaled beta agonists and other measures are crucial for successful treatment. Nevertheless, a few reactions will be fatal whatever treatment is given; optimal management of anaphylaxis is therefore avoidance of the cause whenever this is possible. Predictable cross‐reactivity between the cause of the fatal reaction and that of previous reactions had been overlooked. Adrenaline overdose caused at least three deaths and must be avoided. Kit for self‐treatment had proved unhelpful for a variety of reasons; its success depends on selection of appropriate medication, ease of use and good training.
Association of HLA‐DRB1*07 and DRB1*04 to citrus red mite (Panonychus citri) and house dust mite sensitive asthma
Authors: Cho S.‐H. , Kim Y.‐K. , Oh H.‐B. , Jung J.‐W. , Son J.‐W. , Lee M.‐H. , Jee H.‐S. , Kim Y.‐Y. , Min K.‐U. 
Published: March 2003

BackgroundSpecific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers.ObjectiveThe aim of this study was to evaluate whether susceptibility or resistance to CRM‐induced asthma was associated with HLA‐DRB1 gene.MethodsDNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety‐one adults with CRM‐sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA‐DRB1 alleles were carried out using PCR‐based methods.ResultsAllelic frequency of HLA‐DRB1*07 was higher in the CRM‐sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM‐sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA‐DRB1 gene‐encoded antigens between the two groups.ConclusionHLA‐DRB1 genes may be involved in the development of CRM‐induced asthma. In addition, HLA‐DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM‐exposed adults.
Increased leukotriene production by food additives in patients with atopic dermatitis and proven food intolerance
Authors: Worm M. , Vieth W. , Ehlers I. , Sterry W. , Zuberbier T. 
Published: March 2003

Recently, we identified a subgroup of patients with atopic dermatitis (AD) with a clinical relevant food intolerance proven by double blind placebo controlled challenge. In search of possible pathomechanisms involved in this food intolerance, which leads to aggravation of the disease, the aim of the present study was to determine sulfidoleukotriene production in these patients using isolated leucocytes from the peripheral blood after stimulation with different food additives.Leukotriene production of peripheral leucocytes was detected by incubation of isolated cells with the food additives at different concentrations ranging from 0.2 to 200 µg/mL after pre‐stimulation with IL‐3. Ten non‐atopic donors (A), nine AD patients of the diet responder group with negative oral provocation test against food additives (B) and nine patients of the responder group with positive reactions after the oral provocation test (C) were investigated.In the non‐atopic group (A), no increased sulfidoleukotriene (sLT) release was observed for all food additives tested. In group B, increased sLT production was determined using tartrazine in one patient (1/9) and using nitrite in two patients (2/9), whereas sLT production remained below the cut‐off range in all patients of group B (9/9) using benzoate, metabisulfite and salicylate. By contrast, in group C increased sLT production was observed with food colour mix in 1/9, with tartrazine in 3/9, with benzoate in 4/9, with nitrite in 5/9, with salicylate in 2/9 and with metabisulfite in 1/9. However, no increased sLT concentration was determined in the presence of the tested food additives in two patients of group C.Increased sLT production by peripheral leucocytes in the presence of single food additives was observed in the majority of patients with a proven food intolerance towards food additives proven by double‐blind‐placebo‐controlled challenges. These food additives were particulary tartrazine, benzoate and nitrite. These findings indicate that single food additives as aggravating factors in AD patients may trigger the disease through increased sLT production as a pathophysiological mechanism.
Effect of salmeterol on allergen‐induced airway inflammation in mild allergic asthma
Authors: Boulet L.‐P. , Chakir J. , Milot J. , Boutet M. , Laviolette M. 
Published: March 2003

A previous study suggested that the long‐acting β2‐adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure.To further evaluate the influence of SM on allergen‐induced airway inflammation.We studied, in a randomized, double‐blind, cross‐over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 µg of SM or placebo (P), twice daily for 1 week each, separated by a 2‐week wash‐out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13).As expected, SM improved baseline FEV1 and PC20 (P ≤ 0.009) and decreased the allergen‐induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 ± 23; SM: 161 ± 43, P = 0.031), CD45Ro (P: 37 ± 19; SM: 126 ± 41, P = 0.047) and AA1 positive cells (P: 38 ± 6, SM: 65 ± 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 ± 10; SM: 32 ± 7, P = 0.085), HLA‐DR (P: 65 ± 30; SM: 116 ± 36, P = 0.079) and EG2 positive cells (P: 25 ± 15; SM: 38 ± 26, P = 0.09) tended to increase with SM treatment.In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti‐inflammatory agent, particularly in the context of significant allergen exposure.