The Level of Serum Immunoglobulin E Measured at General Hospitals in Six Regions of Korea in Children with Allergic Diseases / 소아알레르기및호흡기학회지

PURPOSE: We investigated the change in serum total immunoglobulin E (IgE) and allergen-specific IgE according to allergic diseases and age. METHODS: Allergic markers of children under 18 years of age with allergic diseases for the last 5 years were collected from 12 hospitals nationwide. The total data was 9,710. Data about levels of serum total IgE and allergen-specific IgE to 15 common allergens were collected. RESULTS: In children with asthma, serum total IgE was higher in older age than in younger age until age 7 to 12 years, at which time the level was highest (paper radioimmunosorbent test, 526.7 IU/mL; UniCAP, 339.9 IU/mL). The level was lower in older age than that during younger age. This change was similar to that in children with allergic rhinitis and atopic dermatitis. The level was highest at ages 7 to 12 years in children with allergic rhinitis, and at age 10 to 12 years in children with atopic dermatitis. In children with both asthma and allergic rhinitis, as well as in children with all three diseases, the change in serum total IgE was similar to that of children with an isolated disease. The highest level in children with all three diseases was higher than that in children with an isolated disease. The analysis of allergen-specific IgE positivity showed that food allergens were dominant before the age of 2 years, and that aeroallergens such as house dust mites were dominant. CONCLUSION: Serum total IgE in Korean children with allergic diseases was higher in older age than in younger age until the ages of 7 to 12 years, and then the change in total IgE by age was the opposite.

Hymenoptera venom allergy: characteristics, tolerance and efficacy of immunotherapy in the paediatric population.

Hymenoptera venom allergy is a growing problem in Spain. This problem has a special relevance in areas where population is frequently exposed to hymenoptera stings, being paediatric patients a high risk population. Immunotherapy with hymenoptera venom is an effective and safe treatment for these patients. However, there is a lack of data on the role of this treatment on paediatric population. For this reason, from the data base of the Allergy Unit from Hospital Xeral (Lugo, Spain) which includes 560 patients, have been analyzed the 21 paediatric patients, all of them treated with venom immunotherapy. Eighteen patients completed the treatment. The maintenance dose administered was 100 microg. Two systemic reactions (both with an Apis extract) were registered. Cutaneous test and specific IgE shown a statistical significant reduction at the end of treatment (p =.0004 and p <.0001 respectively). Seven patients (33 %) suffered a spontaneous re-stung during maintenance phase or after immunotherapy was completed. In 4 patients there was no allergic reaction and the other 3 children suffered a mild local reaction. In conclusion, venom immunotherapy is a safe and effective treatment in paediatric patients with hymenoptera venom allergy, being necessary to increase the experience on this specific segment of the allergic population.

Prevalence of latex allergy in spina bifida: genetic and environmental risk factors.

AIM OF STUDY: To evaluate the prevalence of latex allergy in a population of children with spina bifida (SB) and to assess the role of early exposure to latex products and others risk factors. INTRODUCTION: SB is related with an higher incidence of latex allergic reactions. These patients received repeated surgical procedures, implant of latex-containing materials and catheterization. MATERIALS AND METHODS: Eighty consecutive subjects affected with SB besides answering a questionnaire, underwent a skin-prick test (SPT) to latex and the determination of the specific serum IgE (RAST CAP) to latex. 40% (32/80) of the patients showed a latex sensitization with specific IgE > 0.7 kU/I but only twelve of the 32 sensitized patients (40%) suffered from clinical reactions to latex (urticaria, conjunctivitis, angioedema, rhinitis, bronchial asthma). Number of surgical procedures, but particularly early exposure to latex and familiarity for allergy are correlated with latex allergy (p < 0.01). CONCLUSION: Latex allergy in SB children is multifactorial situation related with a disease-associated propensity for latex sensitization, early exposure and number of surgical procedures. Prophylactic measures to avoid the exposure, not only in the sanitary environment, through the institution of latex-safe routes and every day, prevent potentially serious allergic reactions.

Use of insulin immunoassays in clinical studies involving rapid-acting insulin analogues: Bi-insulin IRMA preliminary assessment.

BACKGROUND: In clinical studies involving rapid-acting analogues (RAAs), insulin immunoreactivity is frequently measured, including endogenous, regular insulin (RI) and RAA immunoreactivities. Such a procedure implies equivalent cross-reactivities of all insulins present in serum. Commercially available human insulin immunoassays have been widely used, but their limitations (including hemolysis and anti-insulin antibodies) were not fully investigated. The aims of our study were to compare cross-reactivities of RI and RAAs in buffer and in serum and to investigate insulin immunoassay pitfalls. METHODS: Cross-reactivities were assessed using Bi-insulin IRMA (Schering Cis-Bio International) in phosphate-buffered saline (PBS)-1% bovine serum albumin (BSA) and in pools of sera spiked with RI and RAAs (lispro and aspart). To investigate the influence of hemolysis, a pool of sera spiked with RAA was mixed with a concentrated hemolysate (final hemoglobin concentration 10 g/L) and incubated for 3 h at room temperature. To determine interference by anti-insulin antibodies, insulin was removed using charcoal from 18 sera with anti-insulin antibodies and from 17 sera without detectable anti-insulin antibodies. These insulin-free samples were then spiked with RI and RAAs and the immunoreactivity was determined. RESULTS: Compared with buffer, cross-reactivity in serum for RI, lispro and aspart was lower (35%, 29% and 26% lower, respectively). Hemolysis degraded almost all RI and RAAs contained in the serum (>or=95%). Anti-insulin antibody interference was significant for RI and RAAs (p

Glucocorticoid is involved in food-entrainable rhythm of mu-opioid receptor expression in mouse brainstem and analgesic effect of morphine.

The repeated manipulation of feeding schedule has a marked influence on the chronopharmaological aspects of many drugs. In this study, we investigated the role of endogenous glucocorticoid in the mechanism by which restricting the feeding time modulates the analgesic effect of morphine. Male ICR mice were housed under a light-dark cycle (light on from 07:00 to 19:00) with food and water ad libitum or under repeated time-restricted feeding (feeding time from 09:00 to 17:00) for 2 weeks before the experiment. Under the ad libitum feeding, mRNA levels of mu-opioid receptor and its binding capacity in mouse brainstem increased around the early dark phase, following the 24-h variation in circulating glucocorticoid levels. As a consequence, potent analgesic effects of morphine were observed in mice injected with the drug during the dark phase. Daily restricted feeding modulated the time-dependency of mu-opioid receptor function, accompanied by the alteration of the rhythm in circulating glucocorticoid levels. Under the time-restricted feeding, potent analgesic effects of morphine were found in mice injected with the drug during the light phase. Because the manipulation of feeding schedule was unable to produce the food-entrainable rhythm in the expression of mu-opioid receptor in the brainstem of adrenalectomized mice, endogenous rhythm of glucocorticoid secretion seems to be involved in the mechanism by which the time-restricted feeding modulates the analgesic effects of morphine.

[Diagnosis of type I hypersensitivity by laboratory test]. / Diagnostic au laboratoire de l'hypersensibilite immediate.

Type I hypersensitivity is a major problem in public health, often requiring numerous investigations which aim to diagnose atopy and identify the causative allergen. Among these investigations, several blood tests, mostly using immunoenzymatic methods, can be performed to measure total and specific IgE levels. Type I hypersensitivity can also be investigated with assays which quantitate several mediators released after cellular activation induced by allergens.

A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge.

BACKGROUND: Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution. OBJECTIVE: To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo. METHODS: A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC). RESULTS: RAST analysis (n = 14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7-2.4). RAST inhibition (n = 6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0-12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10-200-fold. Hypo-allergenicity was confirmed by DBPCFC (n = 2) with both recombinant molecules. CONCLUSION: A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.

Determination of beta2-microglobulin in biological samples using an immunoenzymometric assay (chemiluminescence detection) or an immunoturbidimetric assay: comparison with a radioimmunoassay.

Monitoring beta2-microglobulin (beta2M) in biological fluids has gained considerable interest in pathologies such as haematologic malignancies, renal diseases, and chronic inflammatory diseases. Due to limitations of the RIA in the routine laboratory, we measure beta2M with non-isotopic methods. 189 patients suffering from myeloma (n=66), end stage renal failure (n=54) or inflammation (n=69) were included in this study. beta2M was determined in serum, urine and dialysate using an immunoenzymometric assay with chemiluminescence detection [Immulite Diagnostic Products Corporation (DPC), La Garenne Colombes, France] and an immunoturbidimetric assay (Olympus, Rungis, France). The data were compared with a radioimmunoassay (Immunotech, Marseille, France) taken as a reference. Using serum samples, the immunoenzymometric assay with chemiluminescence detection and the immunoturbidimetric assay have reliable analytical performances. Values obtained with serum samples are highly correlated with the radioimmunoassay (DPC/RIA r2=0.84; Olympus/RIA r2=0.94) whatever the type of pathology; however an over-estimation which could be related to cross reactivity with beta2M fragments was observed with the RIA method as suggested by crossover calibration and recovery studies. Values obtained with urinary samples (n=96) are closely related to those obtained with the RIA (DPC/RIA r2 = 0.98; Olympus/RIA: r2=0.99). Despite the low levels observed in dialysate (n=57) good correlations were observed between Olympus vs DPC (r2=0.85). By contrast, the two non-isotope methods are poorly related with the RIA method (DPC vs RIA r2=0.47 and Olympus vs RIA r2=0.54). In conclusion, the immunoenzymometric assay with chemiluminescence detection or the immunoturbidimetric assay could be used in the routine laboratory in order to determine beta2M in plasma, urine and dialysate.

[Preclinical diagnosis of renal damage in essential hypertension]. / Doklinicheskaia diagnostika porazheniia pochek pri gipertonicheskoi bolezni.

AIM: To study renal functional reserve and 24-h beta 2-microglobulinuria (B2-MGU) in patients with different stages of essential hypertension (EH) and to evaluate acceptability of these parameters as early markers of preclinical renal impairment in EH. METHODS: We examined 150 patients (mean age 42.1 +/- 3.4 years) with EH without overt clinical manifestations of hypertensive nephropathy. Renal functional reserve (RFR) was determined with the use of acute oral protein loading and was defined as an increase in endogenic creatinine clearance in percent. B2-MGU was evaluated by radioimmunoassay (RIO-BETA-2-MICRO kit). Radioimmunoassay detection of microalbuminuria (MAU) was performed with the use of the standard kit Albumin-RIA. RESULTS: RFR appeared to be significantly lower in patients with EH compared to the control group, and its level significantly decreased with aggravation of EH. Both B2-MGU and MAU were significantly higher in patients with EH and significantly increased with aggravation of EH. CONCLUSION: We suggest that, apart from MAU, RFR abnormalities and excessive B2-MGU should be used as markers of preclinical renal impairment in EH.

Defective regulation of the protective IgE response against intestinal helminth Ascaris lumbricoides in malnourished children.

It is well established that malnutrition affects the immune response and increases the susceptibility to parasitic infection. In the present study we evaluated some aspects of the cellular and cytokine network that regulate the IgE responses, which are important components of host defence mechanisms against helminthic parasites in children infected with the intestinal helminth Ascaris lumbricoides, and with differing degrees of malnutrition. We found a defective T cell response in malnourished children, as indicated by diminished levels of circulating total (CD3+), helper (CD4+), IL-2-receptor-bearing (CD4+CD25+) and memory helper T cell responses (CD4+CD45RO+) in keeping with the decreased specific IgE levels against Ascaris lumbricoides. In contrast, the proportions of total B cells (CD20+), and those bearing the low-affinity IgE receptor (CD23+) were increased in the moderated malnourished children. Moreover, serum IL-4 levels and total IgE were also increased in these children. We suggest that malnutrition can cause an imbalance in T cell subpopulations that may lead to a defective T cell maturation and a decreased specific anti-Ascaris IgE response thus increasing the susceptibility to such infections. The high levels of total IgE observed may be related to a non-specific stimulation of the proliferation of activated B cells, probably caused by helminthic parasites and other infectious agents that are frequent in malnourished children.

Decrease of specific and total IgE levels in allergic patients after BCG vaccination: preliminary report.

BACKGROUND: A systemic reaction to mycobacteria biases the balance of T helper cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics of mycobacterial infection. Children who have undergone tuberculin conversion after BCG vaccination seem to be more likely to lose their atopic symptoms. Inhibition of both allergic response and airway hyperreactivity after vaccination for mycobacteria has been observed in animal experiments. OBJECTIVE: To evaluate the effects that BCG vaccination has on the serological status of allergic people. PARTICIPANTS AND METHODS: This study included 20 volunteers with a history of allergic rhinitis who were required to undergo BCG vaccination by Italian law. Epicutaneous allergy testing with a panel of common seasonal and perennial inhalational allergens and 2 blood withdrawals were performed. The serum total IgE levels and the serum allergen-specific IgE levels of each individual were measured just before BCG vaccination and again 4 months later. Total IgE levels were determined using the paper radioimmunosorbent test, and allergen-specific IgE levels were determined using the radioallergosorbent test. RESULTS: Total IgE and allergen-specific IgE levels were significantly decreased after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION: BCG, an effective stimulus for cell-mediated immunity, deserves further study to evaluate its ability to modulate the immune response associated with allergic rhinitis.

[The formation of the influenza virus aggregates, enriched with hemagglutinin]. / Obrazovanie agregatov virusa grippa, obogashchennykh gemaggliutininom.

The formation of electrostatic aggregates was studied by analysis of two types of virus-containing liquids: initial warm liquid collected at temperature 37 degrees and the same liquid stored over the night at temperature 4 degrees C. The formation of virus aggregates was revealed at 4 degrees C. The aggregates formed at temperature 4 degrees C had a relatively high HA/NP ratio in comparison with unassociated virus analyzed at 37 degrees. HA-enriched aggregates were found in the precipitate formed under short-term high-speed centrifugation as well as in "heavy arm" of the virus profile in the saccharose gradient. Aggregates formed at 4 degrees C dissociated at 37 degrees. The ability to form aggregates is reversible and correlates with the virus concentration. It is shown also that virus containing liquid contains heterogenic structures with molecular weight under 2000 kD having HA involved in the forming aggregates enriching HA. Possible nature of low-molecular HA-containing structures involved in the aggregates and nature of relations stabilizing aggregates are discussed.

Urinary tract infection in full-term newborn infants: risk factor analysis.

OBJECTIVE: To analyze the correlation of risk factors to the occurrence of urinary tract infection in full-term newborn infants. PATIENTS AND METHODS: Retrospective study (1997) including full-term infants having a positive urine culture by bag specimen. Urine collection was based on: fever, weight loss > 10% of birth weight, nonspecific symptoms (feeding intolerance, failure to thrive, hypoactivity, debilitate suction, irritability), or renal and urinary tract malformations. In these cases, another urine culture by suprapubic bladder aspiration was collected to confirm the diagnosis. To compare and validate the risk factors in each group, the selected cases were divided into two groups: Group I - positive urine culture by bag specimen collection and negative urine culture by suprapubic aspiration, and Group II - positive urine culture by bag specimen collection and positive urine culture by suprapubic aspiration. RESULTS: Sixty one infants were studied, Group I, n = 42 (68.9%) and Group II, n = 19 (31.1%). The selected risk factors (associated infectious diseases, use of broad-spectrum antibiotics, renal and urinary tract malformations, mechanical ventilation, parenteral nutrition and intravascular catheter) were more frequent in Group II (p<0.05). Through relative risk analysis, risk factors were, in decreasing importance: parenteral nutrition, intravascular catheter, associated infectious diseases, use of broad-spectrum antibiotics, mechanical ventilation, and renal and urinary tract malformations. CONCLUSION: The results showed that parenteral nutrition, intravascular catheter, and associated infectious diseases contributed to increase the frequency of neonatal urinary tract infection, and in the presence of more than one risk factor, the occurrence of urinary tract infection rose up to 11 times.

[Allergologic explorations in children]. / Explorations allergologiques chez l'enfant.

Guidelines to the multitude of allergologic tests are defined. But, in practical experience, skin prick test are the first and the best test for allergy diagnosis. Positive skin prick test refer to sensitization in accordance with clinical history.

Tear IgE concentrations in allergic conjunctivitis.

PURPOSE: Tear IgE has been considered to play an important role in allergic conjunctivitis and the measurement of tear IgE concentrations can help to diagnose this condition. Locally produced IgE levels have been shown to be the largest contributor to the severity of allergic conjunctivitis. METHODS: One hundred and thirteen allergic conjunctivitis patients (70 seasonal allergic conjunctivitis (SAC), 21 perennial allergic conjunctivitis (PAC), 22 vernal keratoconjunctivitis (VKC)), 14 bacterial conjunctivitis (BC) patients, 13 epidemic keratoconjunctivitis (EKC) patients and 18 normal controls were recruited. Tear samples were collected using the microcapillary method and tear IgE levels were measured using an immunoenzyme assay. RESULTS: Tear IgE concentrations showed significant increases in the VKC (322.2 +/- 45.7 ng/ml), SAC (194.7 +/- 21.7 ng/ml) and PAC (134.8 +/- 23.1 ng/ml) groups when compared with controls (52.1 +/- 9.7 ng/ml, p < 0.01). No significant difference was found between EKC (97.2 +/- 11.7 ng/ml) and BC (92.6 +/- 13.8 ng/ml) groups and controls (p = 0.1). CONCLUSIONS: Tear IgE concentrations showed a significant increase in allergic conjunctivitis patients when compared with controls. Our results suggest that measuring tear IgE concentrations can help to diagnose allergic conjunctivitis.

Inflammation markers and symptom activity in children with bronchial asthma. Influence of atopy and eczema.

BACKGROUND: Eosinophil cationic protein (ECP) has been reported to reflect the eosinophil inflammatory activity in asthma. However, the relative impact of asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has not been established. OBJECTIVES: To examine s-ECP levels and s-myeloperoxidase (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children. METHODS: S-ECP and s-MPO were assessed in relation to symptom activity, lung function, exercise-induced bronchoconstriction and bronchial responsiveness in 101 children; median age 9 years, range 1-16 years; with moderate to severe asthma, admitted to Voksentoppen Center. RESULTS: S-ECP was significantly higher in children with persistent compared to episodic or no asthma symptoms in the past four weeks. S-ECP was also higher in children with atopic compared to non-atopic asthma, as well as in those with active compared to past history or no history of atopic eczema. S-MPO was higher in children with persistent asthma symptoms, but did not differ in relation to atopy or eczema state. Persistent asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and active eczema. CONCLUSION: S-ECP may be used in assessing symptom activity in asthmatic children, but with the realisation that active eczema and the presence of atopy may also influence levels.