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IgE Levels (ige + level)
Kinds of IgE Levels Selected AbstractsExtensive xanthelasma associated with anaplastic large cell lymphoma and hyperimmunoglobulin E syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2003Mi-Woo Lee MD A 57-year-old woman presented with a 6-month history of an extensively spreading, yellowish patch on the periorbital areas and cheeks. A diagnosis of hyperimmunoglobulin E syndrome had been made at the age of 22 years on the basis of an eczematous eruption, recurrent furunculosis, and a persistently elevated immunoglobulin E (IgE) level. Her past medical history revealed that she had suffered from numerous recurrent bouts of chronic sinusitis, otitis media, oral candidiasis, orbital cellulitis, acne rosacea, and pneumonia caused by cytomegalovirus since her twenties. In addition, 1 year ago, anaplastic large cell lymphoma of the cervical lymph node (stage IIIb) developed, and she received six cycles of cyclophosphamide,doxorubicin,vincristine,prednisolone (CHOP) chemotherapy with partial remission. None of her family had any of these problems. Cutaneous examination showed extensive, symmetric, noninfiltrated macular areas of distinct yellow discoloration around the eyes and on both cheeks (Fig. 1). There were also erythematous papulonodular eruptions on the nose and both cheeks, which were thought to be acne rosacea. Laboratory findings were normal, except for an elevated IgE level (8157 IU/mL). Serum concentrations of IgG, IgA, and IgM were normal. Serum complement levels were normal, as evidenced by normal C3, C4, and CH50. Although she had a previous history of a decreased level (12%) of nitroblue tetrazolium (NBT) test (control, 53%), NBT test at our institute was normal. Neutrophil function tests, including neutrophil chemotaxis, neutrophil phagocytosis, neutrophil respiratory burst, and neutrophil microbial killing test, by flow cytometry, showed normal results. The serum lipid levels, including total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were normal. Serum lipoprotein electrophoresis was normal. A biopsy specimen revealed scattered foamy cells throughout the dermis. The larger clusters of foamy cells tended to group around the blood vessels of the dermis (Fig. 2). Figure 1. Extensively distributed, yellowish, flat xanthelasma on the face Figure 2. Clusters of foamy cells around the blood vessels of the dermis (hematoxylin and eosin, ×400) [source] Promoter polymorphism of the IL-18 gene is associated with atopic asthma in Tunisian childrenINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008J. Lachheb Summary Several lines of evidence point to a relevant role of IL-18 in the process of asthma. Some studies suggest that the polymorphism in the gene of IL-18 can be involved in many inflammatory and atopic diseases such as asthma. The aim of our study is to estimate the frequency of the IL-18- 607 C/A (rs 1946518) promoter polymorphism in Tunisian children with asthma. We investigated whether the presence of this polymorphism -607 C/A was associated with asthma or atopy and whether this polymorphism influenced the severity of asthma in affected children. We examined also the relationship between the IL-18 gene polymorphism and the serum total IgE level. The IL-18/-607 C/A polymorphism was analysed by polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis. A total of 105 asthma patients and 112 controls as part of the whole children population were studied in a case-control study. Among the 105 children with asthma, 40 were also studied for linkage analyses with their respective parents. We noted that the A allele was associated with statistically significant increases in the risk of asthma in the case-control study (odd ratio (OR) = 1.55, 95% confidence interval (CI) 1.03,2.33. Moreover, the A allele was also associated with atopic asthma (P = 0.008), but not with asthma severity. The transmission disequilibrium test (TDT) analysis in this family study did not suggest a preferential transmission of the IL-18/ -607 C/A polymorphism to affected children. There is no correlation between the IgE level and the IL-18 - 607 C/A promoter polymorphism. Our data indicate that IL-18 - 607 C/A promoter polymorphism is associated with susceptibility to developing asthma in Tunisian population. [source] The role of selected neuropeptides in pathogenesis of atopic dermatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2008J Salomon Abstract Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation. [source] Respiratory allergy in apprentice bakers: do occupational allergies follow the allergic march?ALLERGY, Issue 4 2004J. Walusiak Background:, This prospective study describes the incidence, risk factors and natural history of occupational respiratory allergy in apprentice bakers. Methods:, Two hundred and eighty-seven apprentice bakers were examined using a questionnaire, skin prick tests (SPTs) to common and occupational allergens, evaluation of total serum IgE level and specific anti-flour and , -amylase IgE, before, 1 year and 2 years after the onset of vocational training. To diagnose occupational respiratory disease, spirometry, histamine and allergen-specific inhalation challenge tests were performed. Results:, The incidence of work-related chest symptoms was 4.2% in the first year and 8.6% in the second year of exposure. Hypersensitivity to occupational allergens developed in 4.6 and 8.2% of subjects, respectively. The incidence of occupational allergic rhinitis was 8.4% after 1 year and 12.5% after 2 years, and that of occupational asthma/cough-variant asthma 6.1 and 8.7%, respectively. The latency period of work-related rhinitis symptoms was 11.6 ± 7.1 months and chest symptoms 12.9 ± 5.5 months. Only in 20% of occupational asthmatics could allergic rhinitis be diagnosed a stage earlier. In 21 out of 25 subjects with occupational asthma, chronic cough was the sole clinical manifestation of the disease. Stepwise logistic regression analysis revealed that positive SPT to common allergens was a significant risk factor of hypersensitivity to occupational allergens (OR = 10.6, 95% CI 5.27; 21.45), occupational rhinitis (OR = 3.9, 95% CI 1.71; 9.14) and occupational asthma (OR = 7.4, 95% CI 3.01; 18.04). Moreover, positive SPT to occupational allergens on entry to the training was a significant risk factor of asthma (OR = 6.9, 95% CI 0.93; 51.38). Conclusions:, The incidence of occupational asthma and rhinitis in apprentice bakers is high and increases z with the duration of exposure. Skin reactivity to common and occupational allergens is the main risk factor of bakers' asthma. Most cases of work-related respiratory symptoms among apprentice bakers are related to a specific sensitization. In most subjects who developed occupational asthma, rhinitis occurred at the same time as the chest symptoms did. [source] Lower levels of plasmacytoid dendritic cells in peripheral blood are associated with a diagnosis of asthma 6 yr after severe respiratory syncytial virus bronchiolitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2009Eli Silver Plasmacytoid dendritic cells (pDC) play a crucial role in antiviral immunity and promoting Th1 polarization, possibly protecting against development of allergic disease. Examination of the relationship between peripheral blood plasmacytoid DC levels and manifestations of asthma and atopy early in life. We have isolated peripheral blood mononuclear cells (PBMC) from 73 children (mean age ± SD: 6.6 ± 0.5 yr old) participating in the RSV Bronchiolitis in Early Life (RBEL) study. Flow cytometry was performed on PBMC detecting DC surface-markers: Blood Dendritic Cell Antigens (BDCA) 1, 3, and 2 which identify myeloid type 1, type 2, and plasmacytoid cells, respectively. Total serum IgE, peripheral eosinophil count, and allergy skin tests were documented. About 45% (n = 33) of study participants had physician-diagnosed asthma by 6 yr of age. These children had significantly lower quantities (mean ± SD) of plasmacytoid DC than their non-asthmatic counterparts (1020 ± 921 vs. 1952 ± 1170 cells per 106 PBMC, p = 0.003). We found significantly lower numbers of myeloid dendritic cells in children with asthma (3836 ± 2472 cells per 106 PBMC) compared with those without asthma (4768 ± 2224 cells per 106 PBMC, p = 0.02); however, this divergence was not significant after adjusting for covariates of age, gender, race, skin test reactivity, smoke exposure, and daycare attendance. We did not identify any direct association between DC levels and markers of atopy: skin test reactivity, peripheral eosinophilia, and IgE level. Children who are diagnosed with asthma after severe RSV bronchiolitis appear to have a relative deficiency of plasmacytoid DC in peripheral blood. [source] Maternal history, sensitization to allergens, and current wheezing, rhinitis, and eczema among children in Costa RicaPEDIATRIC PULMONOLOGY, Issue 4 2002Manuel E. Soto-Quiros MD Abstract Little is known about the factors associated with asthma, allergic rhinitis, and eczema in Latin American countries. We investigated the relation between potential risk factors and current wheezing, allergic rhinitis, and eczema among 208 Costa Rican children aged 10,13 years participating in phase II of the International Study of Asthma and Allergies in Childhood (ISAAC). The geometric mean (,±,SD) serum total IgE level of children with current wheezing was significantly higher than that of children without current wheezing (533.8,±,5.2 vs. 144.7,± 6.0 IU/mL, P,<,0.01). In a multivariate analysis, a maternal history of asthma, skin test reactivity (STR) to house dust mites, and STR to Alternaria were significantly associated with current wheezing. Children who had a maternal history of asthma had 2.4 times higher odds of current wheezing than those without maternal history of asthma (95% CI for OR,=,1.1,5.3). Sensitization to either house dust mite or Alternaria was associated with 3.3 times increased odds of current wheezing (95% CI for OR for STR to dust mite,=,1.6,6.7; 95% CI for OR for STR to Alternaria,=,1.1,11.0). In a multivariate analysis, STR to house dust mite and STR to cat dander were significantly associated with allergic rhinitis, and a maternal history of eczema and STR to dog dander were associated with eczema in the child. The interaction between familial factors and lifestyle changes resulting from social reforms implemented 60 years ago may explain the high prevalence of atopic diseases in Costa Rica. Pediatr Pulmonol. 2002; 33:237,243. © 2002 Wiley-Liss, Inc. [source] Changes in serum lactate dehydrogenase activity in children with atopic dermatitisPEDIATRICS INTERNATIONAL, Issue 2 2010Yasuyuki Morishima Abstract Background:, In recent years an increase has been seen in the number of patients with severe atopic dermatitis (AD) accompanied with generalized typical eruptions. Some markers indicating the severity of the disease and symptom changes are very useful, and therefore the purpose of the present study was to investigate serum lactate dehydrogenase (LDH) as such a marker. Methods:, A total of 58 children with AD were enrolled. The severity of the disease was graded on the basis of the extent of eruptions and the severity of atopic symptoms. The fraction of serum LDH, number of eosinocytes in the peripheral blood, and serum IgE levels were also determined. Results and Conclusion:, There was a close correlation between the severity of cutaneous symptoms and serum LDH activity, and between severity and eosinocyte count, but no relationship was seen between serum IgE levels and severity of the disease. The aforementioned factors were determined in a time-related way. As the patients' condition improved, serum LDH activity tended to decline, but there were no consistent changes in eosinocyte count in the peripheral blood or serum IgE level. On LDH isozyme the levels of LDH4 and LDH5 were high. Tissue showed high LDH activity, especially in epidermides. These results suggest that serum LDH activity is a useful marker. [source] A Korean experience with chronic actinic dermatitis during an 18-year period: meteorological and photoimmunological aspectsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2009Kyu-Won Choi Background and purpose: The authors noted that chronic actinic dermatitis (CAD) increased in connection with increased sun exposure and believed that there may be a correlation between the two. The purpose of this study was to determine the relationship between increased sun exposure and CAD. We also applied a clinical severity scoring system to determine the correlation with various laboratory parameters. Materials and methods: We investigated trends in sun exposure in Pusan during an 18-year period. We conducted photopatch/patch testing in 51 CAD patients. We also determined the total IgE, percentage of eosinophils, and chemokine receptor profiles in the peripheral blood and analyzed correlations between laboratory data and the clinical severity of CAD. Results: A close correlation was demonstrated between the number of CAD patients and increased sun exposure. Positive patch test reactions and positive photopatch reactions were observed in 35 and 41 of the 51 tested patients, respectively. The total IgE levels were higher in the severe group than in the others. CCR4 expression increased in parallel with clinical severity. Conclusion: Korean patients may have increased susceptibility to CAD with increased sun exposure. We believe that the majority of the CAD patients tested had photoallergy and contact allergy. The clinical severity seemed to correlate well with the total IgE level and CCR4 expression. [source] Clinical analyses of atopic dermatitis in the agedTHE JOURNAL OF DERMATOLOGY, Issue 9 2008Ryoji TANEI ABSTRACT The aim of the present study was to analyze the characteristics of atopic dermatitis (AD) in the senile phase. Subjects were comprised of 16 patients investigated for clinical features, serum immunoglobulin (Ig)E levels and skin manifestations. Mean age was 76.9 ± 6.2 years (range, 68,87), with a man : woman ratio of 3:1. Mean age at onset was 67.7 ± 15.7 years. Eight patients (50%) had personal histories of chronic eczema until the young adult phase and three patients (18.8%) showed the classic course of child AD. Eczematous erythroderma in 10 patients (62.5%) and unclassified chronic eczema in five patients (31.3%) were the predominant clinical presentations. Mean total IgE level in sera of the 16 patients was 8810 ± 13 511 IU/mL (range, 5,53 605). Fourteen patients showed positive results for antigen-specific IgE antibodies, and the mean total IgE level for these patients was 10 056 ± 14 044 IU/mL. Specific IgE to the main antigen, Dermatophagoides farinae, was observed in 12 patients (85.7%), representing the principal antibody in eight patients (57.1%). Eczematous dermatitis manifested predominantly in the face and neck, trunk and extensor and flexure sites of extremities, and less commonly in the antecubital and popliteal areas. Other stigmata of AD were observed as follows: red face in 10 patients (62.5%); Hertoghe's sign in six (37.5%); goose-skin in four (25%); facial pallor in three (18.8%); and dirty neck in one (6.3%). These results indicate that senile-type AD represents a characteristic subgroup of AD that appears in the last stage of life in AD patients. [source] Vital role of the itch,scratch response in development of spontaneous dermatitis in NC/Nga miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004K. Mihara Summary Background, The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch,scratch response on the pathology of AD has not been precisely elucidated. Objectives, To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv-NC mice), which are known to be an animal model for human AD. Methods, Capsaicin-sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap-NC mice), and the development of spontaneous dermatitis in the Cap-NC mice was compared chronologically with that in Conv-NC mice. Results, Scratching behaviour was almost completely prevented in Cap-NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap-NC mice were lower than those in Conv-NC mice. Immunological studies showed that the capability of spleen T cells to produce both T-helper (Th) 1 (interferon-,) and Th2 [interleukin (IL)-5 and IL-13] cytokines was diminished in Cap-NC mice. Furthermore, serum levels of IL-18 were approximately twice higher in Conv-NC mice than in Cap-NC mice. Conclusions, These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch-associated scratching behaviour is an effective treatment for AD. [source] Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma familiesCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2004E. Ylikoski Summary Objective T-box expressed in T cells (T-bet) is a transcription factor regulating the commitment of T helper (Th) cells by driving the cells into the Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma or autoimmune diseases. Recent studies have suggested that T-bet might be a candidate gene for asthma. This led us to screen 23 Finnish individuals for single-nucleotide polymorphisms (SNPs) in the T-bet locus and study the association between the SNPs and high serum IgE level and asthma. Methods We screened all six exons, adjacent intronic areas and 2 kb of the 5,-flanking region from 23 individuals utilizing WAVEÔ technology. To explore whether T-bet is associated in serum IgE regulation or asthma we genotyped the SNPs in a Finnish asthmatic founder population. The association analyses were made using haplotype pattern mining. Results Fifteen novel SNPs were found in the T-bet gene. Within the Finnish asthmatic founder population, there was no association between T-bet SNPs and high serum IgE level or asthma. Conclusions The genetic variability in the T-bet gene does not play a role in the pathogenesis of human asthma. Our results provide a novel panel of SNPs in T-bet and will help determine whether the SNPs have a functional role in other T cell-mediated diseases. [source] Specific immunoglobulin E and immunoglobulin G antibodies to toluene diisocyanate-human serum albumin conjugate: useful markers for predicting long-term prognosis in toluene diisocyanate-induced asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2002H.-S. Park Summary Background Our previous study reported that more than 50% of toluene diisocyanate (TDI)-induced asthma patients had persistent asthmatic symptoms even after complete avoidance. Although specific IgE (sIgE) has been detected in a portion of patients with TDI-asthma, a recent investigation suggests that the presence of serum specific IgG (sIgG), not sIgE, is more closely associated with positive bronchoprovocation test (BPT) results. Objective To evaluate the possible role of sIgE and sIgG in predicting long-term prognosis of TDI-asthma. Materials and methods Forty-one TDI-asthma patients whose diagnosis was confirmed by TDI-BPT, and 20 unexposed healthy controls were enrolled. Both sIgE and sIgG to TDI-human serum albumin (HSA) conjugate were detected by ELISA. All patients with persistent asthmatic symptoms took anti-asthmatic medications during the follow-up period (mean: 67.5 months) and were instructed to avoid exposure to TDI. Airway hyper-responsiveness to methacholine (AHM) was monitored every year during the study period. The patients were classified into three groups according to changing patterns of AHM and asthmatic symptoms as follows: group I, no improvement with persistent asthmatic symptoms (n = 12); group II, partial improvement with persistent asthmatic symptoms (n = 13); group III, in remission (n = 16). Results Favourable prognosis was associated with a mild degree of AHM at initial diagnosis (P < 0.05). Although there were no significant differences in the prevalence of sIgE antibody to TDI-HSA conjugate among the three groups (P > 0.05), prevalence of sIgG in group I tended to be higher than in group II (0.05 < P < 0.1). However, the levels of sIgG were significantly higher in group I than in group II (P = 0.05), whereas levels of sIgE were significantly higher in group II than in group I (P = 0.014). No significant differences were noted in exposure duration, sex, age, atopic status, and total IgE level among the three groups (P > 0.05). Conclusion This study confirmed that a favourable outcome is related to a mild degree of AHM and to low levels of sIgG to predict persistent asthmatic symptoms, it also suggested that the presence of high serum-specific IgE at initial diagnosis may represent a better prognosis. [source] Lack of association between a polymorphism in the interleukin-13 gene and total serum immunoglobulin E level among nuclear families in Costa RicaCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2002J. C. Celedón Background IL-13 has been implicated in the pathogenesis of asthma and in the regulation of IgE synthesis in humans. Single nucleotide polymorphisms (SNPs) in the IL-13 gene have been associated with asthma and total serum IgE level in Caucasian populations. Objective To test for genetic association between an SNP in exon 4 of the IL-13 gene (IL-13 + 2044 or Arg130Gln) and total serum IgE level and asthma-related phenotypes in a population with high prevalence of asthma living in Costa Rica. Methods Family-based association study. Results Among 83 Costa Rican school children with asthma and their parents (249 individuals), there was no evidence of linkage disequilibrium between the IL-13 + 2044 SNP and any of the outcomes of interest (total serum IgE level on a logarithmic scale, number of positive skin tests to aeroallergens, and asthma). These results were not significantly changed after adjustment for age and gender. Conclusions No significant evidence of linkage disequilibrium between an SNP in exon 4 of the IL-13 gene and total serum IgE level, sensitization to allergens or asthma was found in a family-based association study in Costa Rica. [source] Human antibody recognition of Anisakidae and Trichinella spp. in GreenlandCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2007L. N. Møller Abstract High levels of total IgE are observed among children in Greenland. To evaluate the extent to which Anisakidae and Trichinella spp. contribute to the high total IgE level, an ELISA and a western blot were developed for the detection of IgG antibodies to Anisakidae, based on excretory/secretory antigens from Anisakidae larvae. Western blots with Anisakidae and Trichinella antigens discriminated between Anisakidae and Trichinella infections, enabling cross-reactivity between the two parasite infections to be eliminated. Serum samples from 1012 children in Greenland were analysed for specific antibodies to Anisakidae and Trichinella. Eleven children were IgG-positive for Trichinella and nine were IgG-positive for Anisakidae, indicating a relatively low prevalence of both infections among children in Greenland. Faecal samples from 320 children were also examined for other intestinal parasites. Enterobius vermicularis was found in one sample and Blastocystis hominis in 32 samples, but no other intestinal parasites were identified. In total, 304 children had elevated total IgE levels. There was a significant association between Trichinella seropositivity and high levels of total IgE, but not between Anisakidae seropositivity and total IgE. The data indicate that parasitic infections alone do not explain the high level of total IgE observed among children in Greenland. [source] CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuliEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Yuichiro Tsunemi Dr. Abstract CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4+ cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-, mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4+ cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4+ cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation. [source] Inefficient processing of mRNA for the membraneform of IgE is a genetic mechanism to limit recruitment of IgE-secreting cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006Alexander Karnowski Abstract Immunoglobulin,E (IgE) is the key effector element in allergic diseases ranging from innocuous hay fever to life-threatening anaphylactic shock. Compared to other Ig classes, IgE serum levels are very low. In its membrane-bound form (mIgE), IgE behaves as a classical antigen receptor on B,lymphocytes. Expression of mIgE is essential for subsequent recruitment of IgE-secreting cells. We show that in activated, mIgE-bearing B,cells, mRNA for the membrane forms of both murine and human epsilon (,) heavy chains (HC) are poorly expressed compared to mRNA for the secreted forms. In contrast, in mIgG-bearing B,cells, mRNA for the membrane forms of murine gamma-1 (,1) and the corresponding human ,4 HC are expressed at a much higher level than mRNA for the respective secreted forms. We show that these findings correlate with the presence of deviant polyadenylation signal hexamers in the 3,,untranslated region (UTR) of both murine and human ,,genes, causing inefficient processing of primary transcripts and thus poor expression of the proteins and poor recruitment of IgE-producing cells in the immune response. Thus, we have identified a genetic steering mechanism in the regulation of IgE synthesis that represents a further means to restrain potentially dangerous, high serum IgE levels. [source] Unified sampling approach for multipoint linkage disequilibrium mapping of qualitative and quantitative traitsGENETIC EPIDEMIOLOGY, Issue 4 2002Fang-Chi Hsu Abstract Rapid development in biotechnology has enhanced the opportunity to deal with multipoint gene mapping for complex diseases, and association studies using quantitative traits have recently generated much attention. Unlike the conventional hypothesis-testing approach for fine mapping, we propose a unified multipoint method to localize a gene controlling a quantitative trait. We first calculate the sample size needed to detect linkage and linkage disequilibrium (LD) for a quantitative trait, categorized by decile, under three different modes of inheritance. Our results show that sampling trios of offspring and their parents from either extremely low (EL) or extremely high (EH) probands provides greater statistical power than sampling in the intermediate range. We next propose a unified sampling approach for multipoint LD mapping, where the goal is to estimate the map position (,) of a trait locus and to calculate a confidence interval along with its sampling uncertainty. Our method builds upon a model for an expected preferential transmission statistic at an arbitrary locus conditional on the sampling scheme, such as sampling from EL and EH probands. This approach is valid regardless of the underlying genetic model. The one major assumption for this model is that no more than one quantitative trait locus (QTL) is linked to the region being mapped. Finally we illustrate the proposed method using family data on total serum IgE levels collected in multiplex asthmatic families from Barbados. An unobserved QTL appears to be located at ,, = 41.93 cM with 95% confidence interval of (40.84, 43.02) through the 20-cM region framed by markers D12S1052 and D12S1064 on chromosome 12. The test statistic shows strong evidence of linkage and LD (chi-square statistic = 18.39 with 2 df, P -value = 0.0001). Genet. Epidemiol. 22:298,312, 2002. © 2002 Wiley-Liss, Inc. [source] Pregnancy, but not the allergic status, influences spontaneous and induced interleukin-1, (IL-1,), IL-6, IL-10 and IL-12 responsesIMMUNOLOGY, Issue 1 2006Petra Amoudruz Summary In this study, we investigated how pregnancy influences cytokine production in response to stimulation of the innate and the adaptive immune system, respectively. Peripheral blood mononuclear cells (PBMCs) from allergic (n = 44) and non-allergic (n = 36) women were collected at three time-points: during the third trimester, at delivery and at a non-pregnant state 2 years after delivery. The production of interleukin-1, (IL-1,), IL-6, IL-10 and IL-12 was measured by enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay (ELISPOT). The spontaneous cytokine production, and the response following stimulation with agents that primarily activate the adaptive part of the immune system [phytohaemagglutinin (PHA), allergen extracts from cat and birch], or lipopolysaccharide (LPS) that activate innate immunity was measured in vitro. There was a significantly higher spontaneous in vitro production of IL-1,, IL-6 and IL-10 by PBMCs during pregnancy than 2 years after pregnancy, and this was not affected by the allergic status of the women. Conversely, in PHA-stimulated cell cultures there was a lower production of IL-10 and IL-12 during pregnancy than 2 years after pregnancy. LPS-induced IL-6 levels were significantly lower in PBMCs obtained during pregnancy than at 2 years after pregnancy. In addition, we made the interesting observation that in allergic women total immunoglobulin E (IgE) levels were significantly lower 2 years after pregnancy compared to the levels during pregnancy. Taken together, our results indicate that while atopic allergy in women does not have a substantial effect on cytokine production, pregnancy has an obvious effect on the immune system in terms of cytokine production as well as on the total IgE levels. [source] A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapyIMMUNOLOGY, Issue 1 2006Patricia Price Summary Low-level production of interferon-, (IFN-,) marks human immunodeficiency virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2 cytokines. This was investigated in two cross-sectional studies of HIV patients who were immunodeficient when they began antiretroviral therapy (ART) and had stable increases in CD4 T-cell counts. Blood leucocytes were assessed unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or mitogen. IFN-, and interleukin (IL)-5 responses were initially assessed by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription,polymerase chain reaction (RT,PCR) system to assess IFN-,, IL-5, IL-4 and IL-4,2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3), CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5 production and IgE levels were elevated in patients. IgE levels did not correlate with IFN-,, but showed an inverse correlation with IL-5 released in culture (P = 0·05). The levels of IL-4, IFN-,, IL-5 and IL-4,2 mRNA were correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN-, mRNA (P = 0·006). Weak positive correlations were evident between CD30 and cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4,2, IL-5 and IFN-, mRNA levels. These analyses provide no evidence for an inverse relationship between T1 and T2 cytokine responses in HIV patients, but suggest that the elevation of IgE marks low cytokine responses. [source] Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+IMMUNOLOGY, Issue 1 2003Mee H. Lee Summary Bisphenol A (BPA) and p -nonylphenol (NP) are representative endocrine disruptors (EDs) that may have adverse effects on human health. The influence of these compounds on allergic immune responses remains unclear. In this study, we have examined the effects of BPA and NP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. Both BPA and NP significantly enhanced IL-4 production in keyhole limpet haemocyanin (KLH)-primed CD4+ T cells in a concentration-dependent manner. Treatment with BPA or NP in vivo resulted in significant increase of IL-4 production in CD4+ T cells and of antigen-specific immunoglobulin E (IgE) levels in the sera of KLH-primed mice. Furthermore, BPA and NP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor (NF)-AT. Activation of T lymphocytes by phorbol 12-myristate 13-acetate/ionomycin resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of BPA or NP, as demonstrated by the electrophoretic mobility shift assay, indicating that the transcription factor NF-AT was involved in the enhancing effect of BPA and NP on IL-4 production. The enhancement of IL-4 production by BPA or NP was significantly reduced by nitrendipine, a blocker of Ca2+ influx, and by FK506, a calcineurin inhibitor. FK506 inhibited the NF-AT,DNA binding activity and IL-4 gene promoter activity enhanced by BPA or NP. These results represent the first report describing possible enhancement of allergic response by EDs through increasing IL-4 production in CD4+ T cells and antigen-specific IgE levels in the sera via the stimulation of Ca2+/calcineurin-dependent NF-AT activation. [source] IgE, allergy, and risk of glioma: Update from the San Francisco Bay Area Adult Glioma Study in the Temozolomide eraINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Joseph L. Wiemels Abstract The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that immunoglobulin E (IgE) levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n = 535 with questionnaire data; 393 with IgE measures) and controls (n = 532 with questionnaire data; 470 with IgE measures). As expected, glioma cases were less likely than controls to report history of allergies [among self-reported cases, Odds ratios (OR) = 0.59, 95% confidence interval (CI): 0.41,0.85]. IgE levels also were lower in glioma cases versus controls (OR per unit log IgE = 0.89, 95% CI (0.82,0.98). However, this inverse relationship was only apparent among cases receiving temozolomide, a treatment which became part of the "standard of care" for glioblastoma patients during the study period. Among patients receiving temozolomide, IgE levels in cases whose blood samples were obtained within 30 days of diagnosis were slightly higher than controls, whereas IgE levels in cases whose blood sample was obtained >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95% CI: 0.71,0.89). Thus, although our results robustly confirm the inverse association between allergy and glioma, the results for IgE are affected by temozolomide treatments which may have influenced IgE levels. These results have implications for the study of immunologic factors in glioma as well as for immunotherapy protocols for treating glioma. © 2009 UICC [source] Fc,RI, gene (FCER1A) promoter polymorphisms and total serum IgE levels in Japanese atopic dermatitis patientsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2010Y. Niwa Summary Two promoter polymorphisms of the high-affinity IgE receptor ,-subunit (Fc,RI,) gene (FCER1A), ,66T>C (rs2251746) and ,315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the ,315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of ,315CT/TT genotype or the ,315T allele was significantly higher in those with highly elevated total serum IgE concentrations. [source] Association between a common IL10 distal promoter haplotype and IgE production in individuals with atopic dermatitisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2009K. Lacy Summary Atopic dermatitis (AD) is a genetically determined inflammatory skin disease characterized by abnormal cytokine production, including increased production of interleukin 10 (IL10). Single nucleotide polymorphisms (SNP) and haplotypes in the IL10 gene promoter region on chromosome 1q31-32 have been implicated in several inflammatory diseases, but generally, only SNPs proximal to the transcription start site (TSS) have been investigated. The aim of this study was to identify proximal, distal and combined haplotype sets in the IL10 promoter region and to study their association with clinical phenotypes in atopic dermatitis. SNPs at positions ,3575, ,2849, ,2779, ,2763, ,1082, ,851, ,819 and ,592 in the IL10 promoter region were genotyped in individuals with atopic dermatitis (n= 47) and nonatopic control subjects (n= 40) using polymerase chain reaction-based techniques and induced heteroduplex generator (IHG) analysis. Pan-promoter, TSS-proximal and TSS-distal haplotypes were reconstructed using phase analysis. Fifteen haplotypes representing all eight SNPs were identified. Subgrouping identified four 4-locus and three 3-locus TSS-proximal haplotypes; and nine 4-locus TSS-distal haplotypes. No difference was found in haplotype or SNP frequencies between the AD and control groups, or between patients with mild or severe disease. However, a common 4-locus TSS-distal haplotype (TGAC) was significantly increased in patients with IgE levels over 1000 kIU L,1. This study is the first to analyse the association between haplotype groups in the IL10 promoter region and clinical phenotypes in AD. We have demonstrated a significant association between the TSS-distal haplotype TGAC, and IgE levels in AD patients. It remains to be shown if there is an association between the TGAC haplotype and IL10 production, which might account for the stimulation of IgE production. [source] Association analysis of polymorphisms in the interleukin-4 receptor (alpha) gene with atopic asthma in patients from western MexicoINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2002K. I. Mújica-López Summary We undertook an association analysis between the ile50val, glu375ala, cys406arg, and ser761pro polymorphisms of the IL-4R, gene and atopic asthma, total IgE levels and IL-4 serum levels in a population from western Mexico. We found that the ser761pro polymorphism was monomorphic for ser761, while there was no association between any of the other polymorphisms and the three phenotypes analysed. [source] Methods for the identi,cation of chemical respiratory allergens in rodents: comparisons of cytokine pro,ling with induced changes in serum IgEJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2003R. J. Dearman Abstract No validated or widely recognized test methods are currently available for the prospective identi,cation of chemicals with the potential to cause respiratory allergy. The cellular and molecular mechanisms that result in the induction of chemical sensitization of the respiratory tract are unclear, although there is evidence for the selective development of T helper 2 (Th2)-type responses and, in some cases, the production of IgE antibody. We have therefore examined the utility of cytokine pro,ling using BALB/c mice, together with the measurement of induced increases in the total serum concentration of IgE in the Brown Norway (BN) rat, as markers for the prospective identi,cation of chemical respiratory allergens. Responses provoked by the reference respiratory allergen trimellitic anhydride (TMA) have been compared with those stimulated by the respiratory sensitizing diisocyanates toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI) and by the acid anhydride hexahydrophthalic anhydride (HHPA). Topical exposure of BN rats to TMA, TDI and HHPA each provoked marked immune activation (increases in lymph node cellularity and proliferation). However, only treatment with TMA stimulated vigorous increases in the total serum concentration of IgE. In contrast, exposure to HHPA, TDI or HDI failed to provoke signi,cant changes in serum IgE concentration or induced only transient and relatively weak increases in serum IgE levels. In parallel experiments using BALB/c strain mice, however, topical application of all four chemical respiratory allergens provoked a marked Th2-type cytokine secretion pro,le in draining lymph node cells. These data suggest that the measurement of induced changes in serum IgE is not suf,ciently sensitive for the robust identi,cation of chemical respiratory allergens. Furthermore, irrespective of the reasons for variations in TMA-induced IgE production among BN rats, doubts remain regarding the utility of these animals for the characterization of immune responses to chemical allergens. Cytokine pro,ling using the BALB/c strain mouse apparently provides a more robust method for the hazard assessment of chemical respiratory allergens. Copyright © 2003 John Wiley & Sons, Ltd. [source] Induced changes in total serum IgE concentration in the Brown Norway rat: potential for identification of chemical respiratory allergensJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2002E. V. Warbrick Abstract A variety of chemicals can cause sensitization of the respiratory tract and occupational asthma that may be associated with IgE antibody production. Topical exposure to chemical respiratory allergens such as trimellitic anhydride (TMA) has been shown previously to induce increases in the total serum concentration of IgE in BALB/c strain mice. Contact allergens such as 2,4-dinitrochlorobenzene (DNCB), which apparently lack respiratory sensitizing potential, fail to provoke similar changes. However, it became apparent with time that there was some inter-animal variation in constitutive and inducible IgE levels. We have now examined the influence of topical exposure to TMA and DNCB on serum IgE levels in the Brown Norway (BN) rat. Such animals can be bled serially and thus it is possible to perform longitudinal analyses of changes in serum IgE concentration. The kinetics of IgE responses therefore can be followed on an individual animal basis, allowing discrimination between transient and sustained increases in serum IgE concentration. Rats (n = 5) were exposed on shaved flanks to 50% TMA, to 1% DNCB (concentrations that elicit comparable immune activation with respect to draining lymph node cellularity and proliferation) or to vehicle alone. Total IgE was measured by enzyme-linked immunosorbent assay in serum samples taken prior to and 14,42 days following initial exposure. Those animals having high pre-existing IgE levels (>1.0 µg ml,1) were excluded from subsequent analyses. The levels of serum IgE in the majority of rats exposed to DNCB or vehicle alone remained relatively stable throughout the duration of all the experiments conducted, although some animals displayed transient increases in serum IgE. Only TMA treatment was associated with a significant and sustained increase in the level of serum IgE in the majority of experiments. The elevated concentrations of IgE induced by topical exposure to TMA are persistent, the results reported here demonstrating that induced changes in IgE are maximal or near maximal at approximately 35 days, with a significant increase in IgE demonstrable for at least 42 days following the initiation of exposure. Interestingly, although TMA and DNCB at the test concentrations used were found to be of comparable overall immunogenicity with regard to lymph node activation and the induction of lymph node cell proliferation, there were apparent differences in humoral immune responses. Thus, not only did exposure to TMA stimulate increases in total serum IgE concentration and the production of specific IgE antibody, but also a more vigorous IgG antibody response was provoked by TMA compared with DNCB. These data suggest that the measurement of induced changes in serum IgE concentration in the BN strain of rat is able to differentiate between different classes of chemical allergen. Given the inter-animal variation in IgE production, it would be prudent to incorporate a concurrent assessment of responses induced by treatment with TMA as a positive control against which to assess the activity of other test materials. Copyright © 2002 John Wiley & Sons, Ltd. [source] An Analysis of Possible Mechanisms of Unexpected Death Occurring in Hydatid Disease (Echinococcosis)JOURNAL OF FORENSIC SCIENCES, Issue 4 2009Roger W. Byard M.B.B.S. Abstract:, Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis. [source] Management of cow's milk protein allergy in infants and young children: An expert panel perspectiveJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9 2009Katrina J Allen Abstract Cow's milk protein allergy is a condition commonly managed by general practitioners and paediatricians. The diagnosis is usually made in the first 12 months of life. Management of immediate allergic reactions and anaphylaxis includes the prevention of accidental food ingestion and provision of an adrenaline autoinjector, if appropriate. By contrast, the clinical course of delayed food-allergic manifestations is characterised by chronicity, and is often associated with nutritional or behavioural sequelae. Correct diagnosis of these non-IgE-mediated conditions may be delayed due to a lack of reliable diagnostic markers. This review aims to guide clinicians in the: (i) diagnostic evaluation (skin prick testing or measurement of food-specific serum IgE levels; indications for diagnostic challenges for suspected IgE- and non-IgE-mediated food allergy), (ii) dietary treatment, (iii) assessment of response to treatment, (iv) differential diagnosis and further diagnostic work-up in non-responders, (v) follow-up assessment of tolerance development and (vi) recommendations for further referral. [source] Early Alteration in Leukocyte Populations and Th1/Th2 Function in Ethanol-Consuming MiceALCOHOLISM, Issue 8 2001Shawn Starkenburg Background: Chronic alcohol consumption polarizes the immune response away from Th1-mediated cell-mediated immunity. In the present report we investigate the first onset of alteration in immune parameters during ethanol consumption in terms of changes in splenic leukocyte cellularity and surface phenotype as well as alterations in Th1 and Th2 function. Methods: BALB/c and C57BL/6 mice were fed ethanol-containing liquid diets, were pair-fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum for up to 12 days. At intervals during the feeding period, splenic leukocytes were assessed for phenotypic markers by flow cytometry and for their ability to support antigen-induced interferon-, (IFN,) production in a coculture system. Mice were bled at intervals throughout the feeding period, and serum immunoglobin E (IgE) and alcohol levels were determined. Results: Data show that phenotypic and functional alterations occur within the first few days of alcohol consumption. Both liquid diets affect splenic cellularity, and by dietary day 5, ethanol-containing liquid diets further reduce B and NK cell numbers. The decline in B cells is accompanied by a concomitant decline in the amount of major histocompatibility complex class II expressed on this population. Functional alteration in Th1-mediated IFN, production occurred in the population fed ethanol-containing liquid diets by dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these unimmunized mice, is increased by dietary day 6 to 8 and correlated with significant blood alcohol levels. Conclusions: Ethanol consumption by mice causes a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function and a rapid increase in systemic IgE levels. [source] Bullous pemphigoid in Liguria: A 2-year surveyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2001E Cozzani Abstract Background The epidemiology of bullous pemphigoid (BP) is not clear because of the heterogeneity of the disease, and its possible association with internal malignancies has been under debate for many years. We report the findings of a 2-year study on incident BP cases in the Liguria region of Italy. Subjects and methods Thirty-two patients with BP were collected over the 2-year period. Diagnosis was made based on clinical findings and confirmed by histology, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) with salt-split skin and monkey oesophagus, and immunoblotting (IB). All patients were thoroughly investigated for possible malignancies and all were followed up for 6 months to monitor the response to treatment. Results DIF showed linear deposits at the dermoepidermal junction in all but one patient. IIF gave positive findings for 15 sera tested with monkey oesophagus and 20 tested with salt-split skin. IB gave positive findings in 19 cases. There was a malignancy in six cases, but no clinical or immunological features that could be considered to predict this occurrence. Conclusions The findings of this study are in accordance with most of the data found in the literature, including the fact that IgG serum levels did not predict the course of the disease. Contrary to previous indications, IgE levels were not indicative of disease course either. Mucosal lesions, erythema multiform-like lesions, negative IIF findings and antibodies to AgPB2 were not a prediction for the development of malignancy. [source] | ||||||||||||||||||||||||||||||||||||||||