Increase In Total IgE Research Articles

Reversibility of bronchial obstruction in patients with primary ciliary dyskinesia to justify correction of inhalation therapy

Purpose. To assess the reversibility of bronchial obstruction in patients with primary ciliary dyskinesia in groups with and without concomitant allergic inflammation, with the aim of a differentiated approach to inhalation therapy and the validity of prescribing bronchodilators.Material and methods. Retrospective analysis of the results of FEV1 before and after inhalation of a bronchodilator and study of the dependence of the reversibility of obstruction on the presence of atopy markers.Results. Of 100 patients, 63% (n=63) had atopy markers; 37% (n=37) did not have these markers (p≤0.05). When comparing the FEV1 indicator in children with the presence of allergic burden (n=63) and in the absence of it (n=37), it was found that in patients with markers of atopy, obstructive changes identified during spirometry were 14.2% more common ( p≤0.05). Reversibility of bronchial obstruction was recorded in 24% (n=24), of which 87.5% (n=21) of patients had markers of atopy (p≤0.05). In children with concomitant allergic burden and a decrease in FEV1, reversibility of obstruction was detected in 48.4% (n=15) of cases (p≤0.05). It was revealed that in patients with the presence of atopy markers and a decrease in FEV1≤80%, reversibility of obstruction occurs 42.8% more often compared to the group of patients with a normal level of FEV1 (p≤0.05).Conclusions. The vast majority of patients with primary ciliary dyskinesia (n=63) have markers of atopy, mainly due to an isolated increase in total IgE in the blood serum (p≤0.05). A decrease in FEV1≤80% in children with allergies was detected 14.2% more often compared to the group of children without it (p≤0.05). In the vast majority of patients with an allergic phenotype, reversibility of obstruction was observed after a test with a bronchodilator. Thus, all patients with primary ciliary dyskinesia and the presence of atopy markers are recommended to undergo a test with a bronchodilator, and if reversibility of obstruction is detected, it is advisable to add a bronchodilator drug to therapy.

Possibilities of allergic reaction therapy in pediatric practice

Introduction. Allergic diseases are a global medical and social problem due to the adverse effect on the physical, psychological and social state of a person. The basic principle of pharmacological therapy of acute allergic diseases is acute urticaria, angioedema (Quincke) – control/elimination of syndromic complexes.Aim. To evaluate the clinical efficacy of the antihistamine dimetindene in the treatment of acute allergic reactions in children.Materials and methods. We analyzed 36 patients aged 3 to 17 years with diagnoses of acute urticaria and acute urticaria with angioedema in a state of moderate severity. Patients felt a violation of the general condition – malaise (88.89%), chills/fever (5.56% and 8.34%, respectively), joint pain (2.78%). All patients underwent general clinical, laboratory and instrumental examination with subsequent analysis of the data obtained. To assess the response to treatment, UAS 7, the CU-Q2oL quality of life questionnaire were used.Results and discussion. The article discusses the main aspects of acute urticaria and angioedema, as the most common nosological forms in patients with atopy. The features of antihistamine therapy and its influence on the stages of the inflammation process are analyzed. The level of eosinophilia in the general blood test (median and interquartile range) was 6.5% (1.3%; 19.1%). An increase in total IgE was recorded in 80.56% of patients. The burden of allergic history was revealed in 86.12% of patients. By the end of the 1st day of treatment, symptoms were absent in every tenth patient (χ2 = 1.2461, p = 0.0865), remained in everyfifth child (χ2 = 53.6152, p = 0.0057) and significantly decreased in 2/3 children under study (χ2 = 59.6281, p = 0.0062). By the end of the 3rd day of therapy with dimetindene in the complex of treatment of acute urticaria and angioedema, a statistically significant improvement in clinical dynamics was recorded (χ2 = 102.1364, p = 0.0041) in the combined assessment of symptoms in 4/5 of the subjects and a decrease in discomfort associated with sleep in the overwhelming majority of the subjects (χ2 =51.4627, p = 0.0036).Conclusion. As a result of our own research on the use of dimetindene in patients with acute allergic reactions, it was shown that dimethindene has characteristics that meet the requirements for the exposure of the therapeutic effect, the level of effectiveness and the safety profile.

Differences between Staphylococcus aureus nasal carriage and IgE-sensitization to Staphylococcus aureus enterotoxin on risk factors and effects in adult population

BackgroundStaphylococcus aureus (SA) nasal carriage (SA carriage) and IgE-sensitization to SA enterotoxin (SE IgE-sensitization) are known to be associated with chronic airway disease.ObjectiveThis study aimed to evaluate the differences in risk factors, type 2 inflammation and respiratory symptoms between SA carriage and SE IgE-sensitization.MethodsWe conducted a cross-sectional study of a community-based adult population to evaluate the environmental exposure and health impact of the Pohang Industrial Complex, Korea. Participants were examined based on self-reported questionnaires, nasal swab, and blood sampling.ResultsThere were 307 participants, and the overall prevalence of SA carriage and SE IgE-sensitization was 26.1% (80/307) and 25.7% (79/307), respectively. An urban environment was significantly correlated with SA carriage, whereas age and obesity were significantly correlated with SE IgE-sensitization. SA carriage was not associated with an increase in total IgE and blood eosinophil count, whereas SE IgE-sensitization was associated with an increased total IgE and blood eosinophil count. SA carriage was significantly correlated with cough persisting for more than three weeks (OR, 3.044; 95% CI, 1.137–8.153) and sputum (OR, 2.429; 95% CI, 1.008–5.854). SE IgE-sensitization was a significant correlation with only sputum (OR, 2.452; 95% CI, 1.066–5.640). SA carriage and SE IgE-sensitization showed a synergistic effect on the prevalence of cough and sputum.ConclusionSA carriage was associated with the urban environment, and SE IgE-sensitization was associated with the elderly and obesity. SA carriage and SE IgE-sensitization had different correlation with type 2 inflammation and airway symptoms.

Asthma-like symptom or "cystic fibrosis asthma"?

The diagnosis of asthma is still a difficult problem in cystic fibrosis. There is no consensus on how to define "CF asthma". The aim of this study was to determine the role of bronchodilator response and laboratory evidence of allergy in "CF asthma". Patients aged ≥6 years with evaluated bronchodilator response and characteristics of atopy were included in the study. Patients diagnosed with Allergic Bronchopulmonary Aspergillosis or pulmonary exacerbation were excluded. A total of 204 CF patients were evaluated, and 40 who met the criteria were included. Asthma had been diagnosed in ten patients. A positive bronchodilator response was present in 47.3% of the patients tested. Aeroallergen sensitization was present in 52.5% of the patients. While the frequency of recurrent/history of wheezing, family history of atopy and elevated total immunoglobulin E were similar (p> 0.05), the frequencies of inhaled medication use and coexistence of asthma were statistically higher in the group with positive allergen sensitization (p<0.05). The frequencies of positive bronchodilator response (77.7% versus 37.9%) and a family history of asthma/atopy (40% versus. 23%) were found to be similar in CF asthma and CF. There were significant increases in total IgE and allergen-specific IgE and an increase in the frequency of aeroallergen sensitization in CF asthma compared to CF (p<0.05). Although not routinely used in the evaluation of patients, allergen specific-IgE and skin prick test for aeroallergen sensitization may be used as an adjunctive test in patients with suspected clinical findings. The recognition of CF asthma may facilitate the development of targeted therapies.

Features of the course of bronchial asthma in children with a history of bronchopulmonary dysplasia

Introduction. The development of bronchial asthma in children is often associated with previous bronchopulmonary dysplasia. Objective . To study the features of the clinical course of bronchial asthma in children with a history of bronchopulmonary dysplasia. Children characteristics and research methods . The test group consisted of 77 patients with a history of bronchial asthma and bronchopulmonary dysplasia. The control group included 81 patients with bronchial asthma without bronchopulmonary dysplasia. The patients were diagnosed in accordance with the Classification of clinical forms of bronchopulmonary diseases in children. The level of immunoglobulins was determined by enzyme immunoassay. Results. The patients with bronchial asthma and bronchopulmonary dysplasia demonstrated an earlier manifestation of bronchial asthma, a mild course and a rare need for inhaled bronchodilators, significant disproportions in changing the level and frequency of allergic inflammation markers — frequent eosinophilia with a lower increase in total IgE. The developed stage-by-stage program of examination and management of children with bronchial asthma and bronchopulmonary dysplasia will improve the diagnosis and treatment of patients with these diseases. Conclusion. The pediatricians shall take into account the identified clinical features of bronchial asthma in children with a history of bronchopulmonary dysplasia in their practice.

The decreased number and function of lymphocytes is associated with Penicillium marneffei infection in HIV-negative patients.

Penicillium marneffei (P. marneffei) infection, which has been traditionally considered as an indicator of immunosuppression, is one of the most common systemic opportunistic infections in patients with AIDS. Recently, more and more P. marneffei infections have been documented in HIV-negative patients without underlying diseases, which challenges the traditional view that P. marneffei infection is an indicator of immunosuppression. We aimed to evaluate the number and function of lymphocytes in HIV-negative patients with P. marneffei infection. 15 HIV-negative P. marneffei-infected patients and 18 healthy controls were recruited and investigated. The number and function of lymphocytes were analyzed by flow cytometry. Most laboratory tests were within the reference ranges, except for a significant increase in total IgE in P. marneffei-infected patients. Lymphocyte subset analysis showed that the number of CD4+ T cells and NK cells was significantly decreased in HIV-negative marneffei-infected patients compared with healthy controls. However, almost half of the marneffei-infected patients still had normal levels of lymphocytes. A further analysis of cell function showed that the activation and proliferation of CD4+ T cells, the cytotoxicity of CD8+ T cells and NK cells, and the cytokine secretion potential of CD4+ T cells and NK cells were all impaired, in comparison with healthy controls. P. marneffei infection has to be regarded as an indicator of immunosuppression. A further investigation of cell function is required in patients with opportunistic infection, as the cell function may be impaired in this condition.

Axenic Caenorhabditis elegans antigen protects against development of type-1 diabetes in NOD mice

Studies in humans and animals have demonstrated that infection with helminths (parasitic worms) is protective against a range of hyperinflammatory diseases. A number of factors limit translation into clinical use, including: potential contamination of helminths obtained from infected humans or animals, lack of batch to batch stability, and potential pathological risks derived from live worm infections. To overcome these limitations we tested whether an antigen homogenate of the non-pathogenic nematode Caenorhabditis elegans confers protection against type 1 diabetes mellitus (T1D) using the Non Obese Diabetic (NOD) mouse model.Our study demonstrates that twice weekly intraperitoneal injections of axenically cultured C. elegans antigen (aCeAg) confers substantial protection against type 1 diabetes in NOD mice. Whereas 80% of control mice (PBS-injected) developed clinical disease, only 10% of aCeAg-treated mice became diabetic. Additionally, aCeAg treated mice had significantly greater numbers of insulin-producing pancreatic islets and greater numbers of islets negative for lymphocyte infiltration. Immunological changes observed in aCeAg treated mice included increases in total IgE and total IgG1, consistent with induction of a type 2 immune response similar to that typically seen in parasitic worm infection. Although evidence suggests that helminth infections induce strong immunoregulatory signals, we did not observe significant changes in regulatory T cell numbers or in production of the regulatory cytokines TGFβ and IL-10. The lack of a regulatory response may be due to our time point of observation, or perhaps the mechanism of aCeAg efficacy may differ from that of helminth infection.Discovery that antigens obtained from a non-parasitic environmental nematode replicate the protective phenotype induced by parasitic worm infections may accelerate our ability to develop nematode-derived therapies for allergy and autoimmune diseases.

THE RELATIONSHIP OF MOLDS SPECIFIC IGE TO TOTAL IGE AND AGE IN MIDWEST PEDIATRIC POPULATION

Introduction Exposures to certain molds can cause disease in human. IgE to common inhalant molds is seen in 10% of population. 50% of those are predicted to have allergic symptoms as a result of exposure to fungal allergens. Relation between mold exposure and increase in total IgE is reported. The aim is to assess whether there is relationship between fungi specific IgE level and age. Methods Laboratory results of 11,073 specific IgE to fungi including Alternaria, Aspergilus, Penicillium, and Cladosporium and 6001 total IgE evaluations were reviewed. Subjects with specific IgE results >0.1 and/or total IgE results >2.0 but Results Mean specific IgE values for Alternaria ranged from 2.6 in under 1 year old children to 15.9 in 14-15 year old children. Mean specific IgE to Aspergillus ranged from 0.8 in 1-2 year old children to 11 in 10-11 year old children. Total IgE values ranged from 15.6 in 3-4 year old children to 39.2 in 14-15 year old children. Both specific IgE to fungus and total IgE trend upward with age with specific IgE rising more sharply during early development. Mean specific IgE appeared to peak at puberty but mean total IgE continued to rise slowly throughout the pediatric period. Conclusions Both mean total and specific IgE against fungi rise as a pediatric population ages with total IgE having a lower rate of increase.

Incidence, Clinical Features and Prognosis of Food Allergy in Children who Underwent Liver Transplantation

Introduction Children suffer from food allergy after liver transplant (LT). We evaluated our 16 years of experience in pediatric patients who developed food allergy after LT Materials and Methods The clinical and laboratory data and clinical outcome of food allergy was evaluated. Total eosinophil count, total IgE and specific IgE levels were measured and skin prick tests were performed. Results A total of 236 pediatric patients received LT at Başkent University from 2001-2017. Food allergy incidence was 8% (19/236) among all patients with LT. All of the patients with food allergy were younger than 3 years of age and food allergy incidence at this group of age was 19.2% (19/99). Twelve patients were male (63.2%). The mean age at the time of LT was 7.92±2.64 months. All of the patients were started on tacrolimus in the posttransplant period. The mean period of time from LT to food allergy was 14.5±13.6 months. Four patients had single food allergy, while 15 patients had multiple food allergies. The allergen was milk in 3 patients and nut in 1 patient with single food allergy. The allergens in patients with multiple food allergy were egg (13 patients, 86.7%), milk (11 patients, 73.3%), nuts (6 patients, 40%), wheat (5 patients, 33.3%), lentil (4 patients, 26.7%), chickpea (4 patients, 26.7%), tropical fruits (3 patients, 20%), red meat (2 patients, 13.3%), soybean (2 patients, 13.3%), sesame (2 patients, 13.3%) and fish (1 patient, 6.7%). The presenting symptoms included diarrhea (13 patients, 68.4%), flushing (12 patients, 63.2%), angioedema attacks (9 patients, 47.4%), bronchiolitis/chronic cough (7 patients, 36.8%) and vomiting (6 patients, 31.6%). One patient with multiple food allergies also had anaphylaxis with lentil ingestion. The total eosinophil count and eosinophil percentage in blood at the time of diagnosis for food allergy were 1853±2876/mm3 and 12.7±10.91%, respectively. Twelve patients had eosinofilia. Total IgE count was 350±411 IU/ml. Nine patients had an increase in total IgE. Milk, egg and wheat specific IgEs were positive in 14 (73.7%), 10 (52.6%) and 7 (36.8%) patients, respectively. Skin prick test was positive for specific allergens in 13 (68,4%) patients. The patients were followed up for a mean period of 4.76±3.97 years. All of the incriminated foods were successfully reintroduced in 7 (36.8%) patients, while only some of the foods were successfully introduced in 8 patients with multiple food allergies. Out of 7 patients who have complete resolution of food allergy, 3 had single food allergy (3/4 patients, 75%) and 4 patients (4/15 patients, 26.7%) had multiple food allergy. Conclusion The development of food allergy after LT is common especially in patients who were transplanted under 3 years of age. Multiple food allergies are more common and they are mostly IgE-mediated. Prognosis is better in single food allergies. Also, milk, egg and wheat were more commonly reintroduced than other foods in multiple food allergies.

In Utero exposure to genistein enhanced intranasal house dust mite allergen-induced respiratory sensitization in young adult B6C3F1 mice.

Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN's developmental immunotoxic effects are increasing. To understand how in utero GEN exposure may modulate postnatal respiratory sensitization, we conducted a time course study using a common household allergen (house dust mites: HDM; 10μg/mouse) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20mg/kg bw). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly doses of HDM extracts, and they were euthanized at day 3 following the final HDM exposure at four different time points (postnatal day (PND) 80, 120, 160, and 200). In utero GEN combined with postnatal HDM exposures (GEN+HDM) increased total IgE production in both young female and male B6C3F1 offspring (e.g., PND 80 in females and PND 120 in males). Increased antigen-specific IgG1, IgG2a and IgG2b levels were also observed at various time points in both female and male offspring. In addition, increases in macrophage number in bronchoalveolar lavage fluid of both female and male GEN+HDM offspring at PND 80 and PND 120, respectively, were observed when compared to the vehicle group. For T cells, an increase over the vehicle in female GEN+HDM offspring was observed at PND 80. Due to similar patterns of increases, it seems likely that GEN+HDM-induced increases in total IgE and macrophages are related. Overall, in utero GEN plus later-life HDM exposures exert increases in total IgE and HDM-specific IgG production as well as macrophage recruitments to the lung in young adult mice.

IL-33 promotes the induction of immunoglobulin production after inhalation of house dust mite extract in mice.

The initial immune response to house dust mite (HDM) is orchestrated by an interplay between epithelial cells (ECs) and dendritic cells (DCs). Innate cytokines released by HDM-exposed ECs activate airway DCs and effector inflammatory cells, which together induce a HDM-specific Th2 cell response. Here, we investigate the respective roles of DCs and IL-33 in sensitization to HDM. Balb/c mice were exposed via the airways to different HDM extracts, differing in at least endotoxin levels [Lotox (LT) and HiTox (HT)]. Alternatively, HDM-pulsed DCs in the presence or absence of additional LT-HDM, or administration of LT-HDM plus recombinant IL-33, were intratracheally (i.t.) administered to induce allergic airway inflammation. Eosinophil recruitment, cytokine production, serum immunoglobulins, and airway histology were analyzed. Direct exposure of airways with HT-HDM induced an eosinophilic airway inflammation, Th2 cytokine production, and an increase in total IgE and HDM IgG1, while LT-HDM was not able to do so. In contrast, i.t. instillation of LT-HDM-pulsed DCs induced a similar airway inflammation, mucus production, and cytokine production, but IgE or HDM IgG1 was not induced. Administration of HDM-pulsed DCs together with LT-HDM, to supply B cells with unprocessed antigen, was not sufficient to induce antibody production. Simultaneous administration of recombinant IL-33 with LT-HDM induced an antibody response, besides a cellular immune response. These results demonstrate that HDM-pulsed DCs were able to drive a Th2 response but that IL-33 was needed to induce a humoral immune response to a single inhalational challenge to HDM.

Longitudinal increase in total IgE levels in patients with adult asthma: an association with poor asthma control.

BackgroundImmunoglobulin (Ig) E is well-known to play a critical role in allergic diseases. We investigated the association between longitudinal change in total IgE level and the asthma control in patients with adult asthma.MethodsFor this retrospective study, 154 patients with asthma aged 21–82 years were recruited from the allergy and pulmonary units of the Showa University Hospital. Data on longitudinal changes in IgE over the preceding 10 years were collected and logarithmically transformed. Associations between longitudinal change in IgE and clinical characteristics including asthma control test (ACT) score, asthma control, pulmonary function test, and antigen specific IgE, were assessed.ResultsPatients with increased IgE tended to have significantly higher mean age, more episodes of acute exacerbation within a year, lower ACT scores, and used oral corticosteroids more frequently than those with decreased or unchanged IgE. The prevalence of uncontrolled asthma was higher in patients with increased IgE than in those with decreased or unchanged IgE. Mean %FEV1 and FEV1% were lower in patients with increased IgE than in those with decreased or unchanged IgE. Moreover, the prevalence of Aspergillus-specific IgE was higher in patients with increased IgE than in those with decreased or unchanged IgE.ConclusionsThese data suggest that a longitudinal increase in total IgE is associated with both poor asthma control and Aspergillus-specific IgE in patients with adult asthma.

Peanut Allergenicity and Cross-Reactivity with Pea Proteins in the In Vivo Model

The aim of the study was to analyse the potential pea-peanut cross-reactivity using the mice BALB/c as a biological in vivo model in the research on immune response to peanut proteins (PnE). BALB/c mice were three-fold sensitised (on days 1, 7, and 21) by oral or intraperitoneal (IP) administration of PnE in 0.5 mg or 1 mg dose, with or without adjuvant – aluminum hydroxide gel (Alum). Serum immunoglobulins (IgE, IgG, IgG1 and IgG2a) and level of cytokines (IL-4, IL-10, IFN- γ), secreted by the isolated lymphocytes were examined. The highest increase in total IgE and peanut-specific IgG1 was noted in the group sensitised by IP administration of PnE in the presence of Alum. Lymphocytes from peanut-sensitised (with and without Alum) mice showed a significantly high level of IL-4 and this cytokine was secreted to a much higher extent as compared to IFN- γ. Stimulation of a culture of lymphocytes with pea proteins resulted in high IFN-γ secretion. A weak reaction of peanut-specific IgG1 present in mice serum with pea globulins (vicilin – PV and legumin – PL) can suggest that the cross-reactivity between peanut and pea proteins results from the presence of proteins other than 7S and 11S globulins. Due to the demonstrated low cross-reactivity between peanut proteins and pea globulins, the possibility of applying pea proteins in peanut-allergy immunotherapy may be suggested.

Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis

S U N D A Y 366 Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis Inmaculada S anchez-Mach in, MD, Paloma Poza, Ruperto Gonz alez, Victor Matheu, MD; Hospital Ofra-T orax, Tenerife, Spain, Hospital Ofra-T orax, santa cruz de tenerife, Spain, Hospital Ofra-T orax, S/C de Tenerife, Spain, Hospital Ofra, Tenerife, Spain. RATIONALE: Allergen sensitization appears to be part of the etiology of Atopic Dermatitis (AD). The effectiveness of allergen specific immunotherapy (SIT) in AD remains controversial, even contraindicated in severe cases. METHODS: Total IgE (T-IgE) and Specific IgE (S-IgE) by CAPFarmacia. Patient 1 (P1): 43-year-old male. Patient 2 (P2): 31-year old woman. Patient 3 (P3): 9-year-old woman. All of them were nonresponders to usual therapeutics including corticosteroids oral (Last year daily for P1, P2, and 6 cycles for P3), cyclosporin (P1, P2) or methotrexate (P1with bloody diarrhea). They hadmild persistent rhinitis and intermitent asthma and positive S-IgE to Dermatophagoidesand storage mites, and P1 also to grass, ragweed pollen and foods without clinical relevance. RESULTS: In a first visit SCORAD and T-IgEwere: P1, 81 and 31,090UI/ ml. P2, 75 and 19,038UI/ml. P3, 36 and 14.897UI/ml.We started treatment with SIT, with cluster administration schedule of 4weeks in Hospital Immunotherapy Unit and subsequent monthly maintenance. The early months P1 and P2 showed improvement. The T-IgE was descending in improved patients to be in the 4 year of SIT: 5,560UI/ml for P1 and 2,500UI/ml for P2 with SCORAD of 11 and 5 respectively. However, since there was no clinical improvement for P3 over the first year and her T-IgE increase to 19,239UI/ml and SCORAD to 40, the SIT was stopped. CONCLUSIONS:Wehave observed a rapid onset of action after initiation of SIT in some cases of Severe AD. Clinical improvement was correlated with the decrease in T-IgE. The SIT may be a therapeutic alternative.

A Randomized, Open-Label, Parallel Group Study to Evaluate the Efficacy and Safety of Proactive Management in Pediatric Subjects with Moderate to Severe Atopic Dermatitis

S U N D A Y 366 Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis Inmaculada S anchez-Mach in, MD, Paloma Poza, Ruperto Gonz alez, Victor Matheu, MD; Hospital Ofra-T orax, Tenerife, Spain, Hospital Ofra-T orax, santa cruz de tenerife, Spain, Hospital Ofra-T orax, S/C de Tenerife, Spain, Hospital Ofra, Tenerife, Spain. RATIONALE: Allergen sensitization appears to be part of the etiology of Atopic Dermatitis (AD). The effectiveness of allergen specific immunotherapy (SIT) in AD remains controversial, even contraindicated in severe cases. METHODS: Total IgE (T-IgE) and Specific IgE (S-IgE) by CAPFarmacia. Patient 1 (P1): 43-year-old male. Patient 2 (P2): 31-year old woman. Patient 3 (P3): 9-year-old woman. All of them were nonresponders to usual therapeutics including corticosteroids oral (Last year daily for P1, P2, and 6 cycles for P3), cyclosporin (P1, P2) or methotrexate (P1with bloody diarrhea). They hadmild persistent rhinitis and intermitent asthma and positive S-IgE to Dermatophagoidesand storage mites, and P1 also to grass, ragweed pollen and foods without clinical relevance. RESULTS: In a first visit SCORAD and T-IgEwere: P1, 81 and 31,090UI/ ml. P2, 75 and 19,038UI/ml. P3, 36 and 14.897UI/ml.We started treatment with SIT, with cluster administration schedule of 4weeks in Hospital Immunotherapy Unit and subsequent monthly maintenance. The early months P1 and P2 showed improvement. The T-IgE was descending in improved patients to be in the 4 year of SIT: 5,560UI/ml for P1 and 2,500UI/ml for P2 with SCORAD of 11 and 5 respectively. However, since there was no clinical improvement for P3 over the first year and her T-IgE increase to 19,239UI/ml and SCORAD to 40, the SIT was stopped. CONCLUSIONS:Wehave observed a rapid onset of action after initiation of SIT in some cases of Severe AD. Clinical improvement was correlated with the decrease in T-IgE. The SIT may be a therapeutic alternative.

Safety evaluation of genetically modified mustard (V4) seeds in terms of allergenicity

Genetically modified (GM) mustard line (V4) with increased carotenoid content was compared with native mustard to find the difference in allergenic potential, if any. Simulated gastric fluid (SGF) digestibility of crude protein extract from GM as well as its native counterpart mustard crop was envisaged to understand the intended or unintended changes in GM crop along with IgE immunoblotting. BALB/c mice were used as model for allergenicity studies for monitoring total and specific IgE, specific IgG1, histamine level, histopathology, and systemic anaphylaxis score. Allergenicity of mustard was checked in humans by clinical history, skin prick test and IgE levels. Similar results were evident by significant increase in total IgE, specific IgE, IgG1, histamine levels, in GM and native mustard in comparison to control group. Prominent anaphylactic symptoms (score 2: 60%; score 3: 20%; score 4: 20% in native mustard and score 2: 40%; score 3: 40%; score 4: 20% in GM mustard) and eruptive histopathological changes were observed in both GM and native mustard when compared with controls. One protein of approximately 16 kDa was found stable up to 1 h in both GM as well as non GM mustard. IgE immunoblotting detected three protein components of approximately 29, 24 and 16 kDa in both GM and non GM varieties. Collectively, our data demonstrate substantially equivalent allergic responses against GM as well as its native counterpart. Therefore, the GM mustard may be as safe as its native counterpart with reference to allergenic responses.

Risks of Exposure to Occupational Asthmogens in Atopic and Nonatopic Asthma

Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy. We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function. We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (≥100 U/ml) or a positive Phadiatop test (≥0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix. We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8-8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6-4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8-21.8; and AOR, 4.1; 95% CI, 1.3-13.0, respectively). The ratio of FEV₁ to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma. In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma.

Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde.

Hydrocortisone enhances total IgE levels—but not the synthesis of allergen-specific IgE—in a monocyte-dependent manner

Recently, hydrocortisone (HC), when combined with human IL-4, has been reported to increase IgE levels in supernatants (SN) of in vitro cultured leucocytes. In this study we investigated the influence of HC on allergen-specific IgE synthesis. Moreover, we examined the relevance of different cell types in this respect. Peripheral blood mononuclear cells (PBMC), T-cell depleted PBMC, CD14-depleted PBMC and highly purified B cells from 10 allergic (birch pollen and/or grass pollen) patients and five non-allergic individuals were investigated. The cells were incubated with HC and/or recombinant human IL-4 (rIL-4) for 8 days. A considerable increase of total IgE was observed in HC/rIL-4-stimulated cultures compared with rIL-4 alone, HC alone or non-stimulated cultures. We demonstrate that this effect depends on the presence of monocytes in in vitro cultures. These results were seen in every experiment, irrespective of healthy or atopic state of the blood donor. The increase of IgE could not be attributed to a rise of birch pollen-and/or grass pollen-specific IgE in patients allergic to these allergens, as shown by IgE-immunoblot. Radio-allergosorbent test (RAST) investigations of HC/rIL-4-stimulated cells cultures from allergic and non-allergic patients confirmed that HC/rIL-4-induced elevated IgE production was also not due to increased production of IgE, specific for important aero-allergens (pollens, house dust mite or animal dander). Therefore we conclude that newly synthesized IgE is not specific for allergens, but that sequential isotype switching in human B cells leads to increased polyclonal IgE production.

Exposure to the Immunosuppresant, Perfluorooctanoic Acid, Enhances the Murine IgE and Airway Hyperreactivity Response to Ovalbumin

These studies were conducted to investigate the role of dermal exposure to perfluorooctanoic acid (PFOA), a known immunosuppressant, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. PFOA has had widespread use as a carpet and fabric protectant. BALB/c mice were exposed dermally, on the dorsal surface of each ear, to concentrations of PFOA ranging from 0.01 to 1.5% (applied dose 0.25-50 mg/kg) for 4 days. In hypersensitivity studies, mice were also ip injected with 7.5 microg OVA and 2 mg alum on days 1 and 10 and in some studies challenged with 250 microg OVA by pharyngeal aspiration on days 17 and 26. Following exposure to PFOA, an increase in liver weights and a decrease in thymus and spleen weights and cellularities were observed. Similar immunomodulatory trends were demonstrated in mice coadministered PFOA and OVA. Compared to the OVA alone-exposed animals, an increase in total IgE was demonstrated when mice were coexposed to OVA and concentrations of PFOA ranging from 0.75 to 1.5%, while the OVA-specific IgE response peaked with 0.75% PFOA coexposure (p < or = 0.05). OVA-specific airway hyperreactivity was increased in the 1.0% PFOA coexposed group (p < or = 0.05), with an increased pleiotropic cell response characterized by eosinophilia and mucin production, in animals coexposed to concentrations of PFOA up to 1.0%, as compared to the OVA alone-exposed animals. In a murine model, PFOA was demonstrated to be immunotoxic following dermal exposure, with an enhancement of the hypersensitivity response to OVA, suggesting that PFOA exposure may augment the IgE response to environmental allergens.