Atopy and IgE in a pediatric allergy practice

In children under six years of age referred to a pediatric allergy practice the usefulness of serum IgE assay was evaluated in relation to age, symptoms, nasal eosinophilia, skin tests and family history. In more than 60% of the children the initial symptom, usually rhinorrhea, had occurred before one year of age. In infancy the diagnosis was more difficult, gastrointestinal complaints were more frequent and nasal eosinophilia less frequent than in the older children. Many infants had positive skin tests to foods and to environmental allergens. There was a significant correlation between elevated serum IgE level and age, nasaeosinophilia, the number of positive skin tests and the probability of immunotherapy being prescribed. Although no clear diagnostic level is seen, an IgE level above 100 micron/ml at any age and an IgE level above 20 micron/ml in infants strongly suggest the possibility of atopic disease. However, a low IgE level does not exclude atopic disease.     

Spontaneous IgE production in asthmatic children

In this study, we demonstrated spontaneous IgE production by peripheral blood mononuclear cells of asthmatic children. In 26 asthmatic children, the level of spontaneous IgE ranged 0.1-15.0 IU/ml and in 5 healthy normal children showed under 0.051 IU/ml. In 5 of asthmatic children, specific antibody of Dermatophagoides farinae was detected from PBMC by CAP RAST. In healthy normal children, specific antibody of Df was not detected. Spontaneous IgE production by PBMC and serum IgE level showed well correlation (gamma = 0.835, p < 0.001). Spontaneous IgE production and specific antibody of Df by PBMC also showed well correlation (gamma = 0.717, p < 0.001) IgE production of asthmatic children was inhibited by IFN-gamma.     

Clinical study of children with nasal allergy

Possible factors influencing nasal allergy in children were studied using a questionnaire and allergic examination including eosinophil count of nasal discharge, IgE RAST score to house dust and provocation test. We investigated three groups of children according to the results of allergic examinations. The negative group, the equivocal group and the definite group, respectively, consisted of 40, 49 and 107 children. We found the prediction value of definite group with eosinophil count of nasal discharge, IgE-RAST score and provocation test to house dust were respectively 77.0, 89.2 and 78.1%. Bottle feeding and history of asthma bronchiale occurred more frequently in the definite group. These observations provide epidemiologic and clinical bases for further investigations of children with nasal allergy.     

Stem cell factor mRNA expression and production in human nasal epithelial cells: contribution to the accumulation of mast cells in the nasal epithelium of allergy

BACKGROUND: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. OBJECTIVE: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. METHODS: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed-PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. RESULTS: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/beta-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects (P =. 0424, P =.0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells (r = 0.506, P =.0023) and the histamine content (r = 0.480, P =.0040). CONCLUSIONS: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose.     

Screening for IgE mediated allergy among people working in the Marseilles harbour

Clinical application of colony-stimulating factors (CSFs) such as recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) are advancing rapidly now that these factors are approved as indicated therapy in patients with chemotherapy-induced neutropenia, patients undergoing autologous bone marrow transplantation (BMT) and patients who develop graft failure after BMT. Novel CSFs are also being explored for potential clinical application in situations not as significantly affected by rhG-CSF or rhGM-CSF. Studies determining unique effects of novel factors, combinations of factors and combinations with peripheral blood progenitor cell fusions which may lead to future clinical applications of CSFs will be reviewed.     

Cytokine production in children outgrowing hen egg allergy

BACKGROUND: Approximately 40 to 80% of egg-allergic children outgrow egg allergy after 2 to 5 years. OBJECTIVE AND METHODS: To detail the immunologic mechanisms involved in the development of tolerance to egg proteins, the balance between interleukin 4 (IL4) and interferon-gamma (IFN-gamma) synthesis in patients with active atopic dermatitis allergic to hen egg and in those outgrowing hen egg allergy was evaluated. RESULTS: A marked increase in IL4 and a decrease in IFN-gamma synthesis by peripheral blood lymphocytes following ovalbumin (OVA) specific in vitro stimulation was observed in active atopic dermatitis. In contrast, OVA-induced IL4 synthesis in patients in remission was comparable to that in normal individuals. An intriguing finding was higher production of IFN-gamma by lymphocytes from ovalbumin-insensitive patients in remission as compared to normal individuals following antigen stimulation, although cell proliferation in OVA-stimulated lymphocytes was reduced in patients during remission. CONCLUSION: OVA antigen may be capable of inducing a population of Th1-type cells to produce cytokines such as IFN-gamma, resulting in suppression of Th2-type responses, i.e. IL4 secretion. We speculate that the changes in the balance of relevant antigen-induced cytokine synthesis seen in such patients may be causally associated with the improvement in their clinical status.     

Intravenous immunoglobulin inhibits IgE production in human B lymphocytes

This study sought to determine the prevalence of spontaneous reperfusion of an infarct-related artery (IRA) and associated myocardial salvage in the absence of thrombolysis or angioplasty. Twenty-one patients with acute myocardial infarction received only heparin and aspirin. At a median of 18 hours after presentation, 12 patients (57%) had angiographic patency of the IRA. Technetium-99m sestamibi was injected acutely on presentation and again at hospital discharge. Acute and final perfusion defect sizes were measured. Their difference, myocardial salvage, was calculated along with salvage index (myocardial salvage/acute defect). Comparing patients with a patent versus occluded IRA, myocardium at risk was similar (16% +/- 12% vs 12% +/- 9% left ventricle, p = NS); however, myocardial salvage (9% +/- 9% vs -2% +/- 7% left ventricle, p = 0.01), and salvage index (0.62 +/- 0.37 vs 0.19 +/- 0.33, p = 0.01) were greater in patients with spontaneous reperfusion. Resolution of chest pain was greater in patients with a patent IRA (100% vs 55%, p = 0.003). Spontaneous reperfusion of the IRA occurs frequently in patients with acute myocardial infarction and is associated with significant myocardial salvage.     

Anti-schistosomal IgE and its relation to gastrointestinal allergy in breast-fed infants of Schistosoma mansoni infected mothers

To study the relationship between presence of gastrointestinal allergic manifestations in breast-fed infants and presence of IgE against Schistosoma mansoni antigens, sixty breast-fed infants of S. mansoni infected mothers were selected. Of them, thirty infants were suffering from manifestations of gastrointestinal allergy (patients) and the other thirty were not suffering from such manifestations (controls). Levels of IgE against S. mansoni adult worm antigen (AWA), soluble egg antigen (SEA) and cercarial antigen (CA) were determined, by ELISA, in sera of these infants. There was significant association between presence of allergic manifestations and presence of IgE against AWA (P = 0.018), SEA (P < 0.001) and CA (P = 0.002). Also, concentration of IgE against AWA was significantly higher in patients group than the control group (P = 0.024). IgE against AWA showed significant negative correlation with haemoglobin concentration (P = 0.009) and serum albumin level (P = 021) and significant positive correlation with absolute eosinophilic count (P = 0.005). Also, IgE against CA showed significant negative correlation with haemoglobin concentration (p = 0.047) and serum albumin level (0 = 0.036). It was concluded that gastrointestinal allergy in breast-fed infants of S. mansoni infected mothers may be due to hypersensitivity of Schistosoma mansoni antigens present in mothers' milk. Schistosoma mansoni should be investigated and treated in mothers from endemic localities when their breast-fed infants are suffering from manifestations suggestive of gastrointestinal allergy.     

Induction of IgE antibody production in mice with different DPT-vaccine preparations

A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow-up of 6.8 years (range 1 month-22 years) was realized. Compared to the non-diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95% CI 1.34-2.30) and a higher mortality rate (risk ratio 1.54, 95% CI 1.07-2.23). Mortality after 10 years was 36% vs 20% (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65-74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95% CI 1.24-3.37).     

Comparison of skin-prick test and specific serum IgE determination for the diagnosis of latex allergy

The synthesis and anticonvulsant activity of novel 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones 3a-e, structurally-related to GYKI 52466 1, a well-known noncompetitive AMPA-receptor antagonist, are reported. The new compounds possess marked anticonvulsant properties and, in analogy to 1, antagonize seizures induced by AMPA. In addition, when compared to the model compound 1, compounds 3 show a longer-lasting anticonvulsant activity and a lower toxicity.     

Codfish allergy in adults. Specific tests for IgE and histamine release vs double-blind, placebo-controlled challenges

BACKGROUND: At present, several in vitro tests for immunoglobulin E (IgE)-mediated food allergy are available. An estimation of the diagnostic accuracy of the various tests used in predicting clinical sensitivity to codfish in a well-characterized allergic material is necessary. OBJECTIVES: To compare the diagnostic value of four specific IgE tests, and histamine release from basophils (HR) in identifying clinical type I allergy to codfish. As a true diagnosis, double-blind, placebo-controlled food challenges (DBPCFC) were employed. METHODS: Eight clinically codfish-allergic adult patients were investigated together with 30 codfish-tolerant control subjects for evidence of codfish-specific reactivity by Phadebas RAST (PHA), Pharmacia CAP System RAST (CAP), Magic Lite (ML) and HR. To characterize the diagnostic properties of a freshly prepared raw codfish extract, experiments were conducted employing an in-house radioallergosorbent test (RAST), the Maxisorp RAST (MAXI) and HR. Finally, protein profile and IgE-reacting allergens were detected by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: The sensitivities of HR with commercial extract and the three commercially available specific IgE analyses were 0.83 and 1.00 respectively. Specificities were 1.00 (HR) and 0.87-1.00 (specific IgE tests). Freshly prepared codfish extracts improved the sensitivity of HR. SDS-PAGE revealed approximately 29 bands (< 14.3-200 kDa) including a band of 12-13 kDa, and in immunoblotting 18 sera identified 17 IgE-binding bands. The protein migrating at 12-13 kDa was identified in the fresh codfish extract tested with sera from all clinical codfish allergics, while no significant reaction was seen in the control subjects. CONCLUSION: Based on the small number of adult patients included in our study, the in vitro assays with commercial and fresh extracts have high sensitivity and are acceptable for screening for codfish allergy. Specificity of Phadebas, CAP, and our in-house RAST was less than unity, whereas ML and strong binding of IgE to a 12-13 kDa protein completely matches DBPCFC results, and thus seems sufficient for establishing the diagnosis.     

Chemical respiratory allergy, IgE and the relevance of predictive test methods: a commentary

Polycystic ovary syndrome is a diagnosis made in 5%-10% of women between late adolescence and the menopause. Patients may present with oligomenorrhoea or amenorrhoea, anovulation or infertility, hirsutism or acne. Women with the syndrome have at least seven times the risk of myocardial infarction and ischaemic heart disease of other women, and by the age of 40 years up to 40% will have type 2 diabetes or impaired glucose tolerance. Polycystic ovary syndrome is associated with insulin resistance, with consequent hyperinsulinaemia and (frequently) hyperlipidaemia and obesity. Recent research has shown that the application of diabetes management techniques aimed at reducing insulin resistance and hyperinsulinaemia (such as weight reduction and the administration of oral hypoglycaemic agents) can not only reverse testosterone and luteinising hormone abnormalities and infertility, but can also improve glucose, insulin and lipid profiles. The management of polycystic ovary syndrome should now include patient education and attention to diabetes and cardiovascular risk factors such as hyperlipidaemia, obesity, physical exercise, glucose intolerance, hypertension and cigarette smoking.     

Rhinomanometry, sinus CT-scan and allergy testing in the diagnostic assessment of chronic nasal obstruction

In order to assess how effective a combination of diagnostic methods, each addressing specific aetiopathogenic aspects, would be in uncovering the cause of common chronic nasal obstruction, we evaluated 45 consecutive adult subjects. They were submitted to rhinomanometry testing, sinus CT-scans and RASTs to prevalent allergens. Most, but not all, patients ended up showing abnormal results in at least one of the diagnostic procedures. Sinus pathology was, by far, the most frequent diagnosis, while allergy took second place, with a number of atopic subjects displaying sinusitis as well. On the other hand, septal deviations with a significant effect on nasal resistance were only seldom found to be the cause of chronic nasal obstruction.     

Combined nasal challenge with diesel exhaust particles and allergen induces In vivo IgE isotype switching

In this study we undertook to provide evidence for local in vivo isotype switching to IgE following nasal challenges. Detection of deleted switch circular DNA (switch circles) by a novel nested polymerase chain reaction-based approach was employed as definitive molecular evidence of Ig isotype switching. Nasal challenge in humans with diesel exhaust particles (DEP) plus ragweed antigen has been shown to enhance local IgE production, stimulate local cytokine production, and markedly increase mucosal IgE antibody to ragweed. Four days after combined intranasal DEP plus ragweed challenge, we detected and characterized clones of deleted switch circular DNA (Sepsilon /Smu) representing switching from mu to epsilon from nasal lavage cells. No switch circular DNA was detected in nasal lavage cells following challenge with DEP alone nor with ragweed allergen alone. These results indicate that the combination of mucosal stimulation with DEP and ragweed allergen is capable of driving in vivo isotype switching to IgE in humans with ragweed allergy. These results are the first direct demonstration of in vivo IgE isotype switching in humans.     

Quantitative measurement of nasal production of nitric oxide in awake humans

The aim of this study was to determine, quantitatively, the production of nitric oxide (NO) in the nose and nasopharynx. Subjects were instructed to perform a Valsalva manoeuvre with their mouth open as gas was aspirated from a closely fitting nasal CPAP mask by a chemiluminescence analyser (Sievers 270B, Sievers Instrument Corp. Boulder, Colorado, U.S.A.). Room air was free to flow in through the mouth and out through the nose and hence to the analyser. The manoeuvre was continued until a smooth plateau of at least 20 seconds in duration was achieved on a chart recorder. The mean plateau concentrations were 176 (+/- 39.6) parts per billion (ppb) for males and 135.8 (+/- 24.4) ppb for females. The mean male production of NO was 15.8 nanomol/min which was significantly different from that of females of 12.5 nanomol/min (Mann-Whitney U Test; P < 0.01). By measuring the concentration of NO in gas aspirated from the nose during Valsalva manoeuvre, we excluded the respiratory tract below the glottis from our sampling and as such results represent the portion of NO produced in the nose and nasopharynx. These findings suggest that nasally produced NO is produced in sufficient quantities to act as a continuous pulmonary vasodilator, being inspired preferentially into areas of greatest ventilation, thus perhaps acting to continually match ventilation to perfusion.