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1.
Inheritance of total serum IgE (basal levels) in man.   总被引:7,自引:3,他引:4       下载免费PDF全文
Since allergic individuals with atopic allergy tend to have higher total serum IgE levels than do nonallergic subjects, family studies of total serum IgE levels are necessary in delineating the genetic and environmental factors involved in the expression of allergic disease. However, previous studies do not agree as to the genetic basis of total IgE production. To try to resolve this conflict, a total of 278 individuals from 42 nuclear families ascertained for large family size (at least four children) were studied. The families were not selected for the presence of allergic disease. Segregation analysis showed that the mixed model of recessive inheritance of high levels was most appropriate for these data--with approximately 36% of the total phenotypic variation in log[IgE] attributable to genetic factors, equally divided between a Mendelian component and a more general polygenic component. Thus, these data suggest some role for Mendelian control of basal IgE levels, but there is significant familial aggregation in IgE levels over and above that due to a Mendelian factor.  相似文献   

2.

Objectives

A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.

Methods

Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed.

Results

A total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4.

Conclusions

Sensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood.  相似文献   

3.

Background

Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA.

Methods

Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE.

Results

Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores.

Conclusions

These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.
  相似文献   

4.
Immunoglobulin E (IgE) isotype antibodies are associated with atopic disease, namely allergic rhinitis, asthma and atopic dermatitis, but are also involved in host immune defence mechanisms against parasitic infection. The commitment of a B cell to isotype class switch to an IgE-producing cell is a tightly regulated process, and our understanding of the regulation of IgE-antibody production is central to the prevention and treatment of atopic disease. Both those that are presently in use and potential future therapies to prevent IgE-mediated disease take advantage of our existing knowledge of the specific mechanisms that are required for IgE class switching.  相似文献   

5.

Objectives

Leukotrienes play a central pathophysiological role in allergic asthma. The aim of this study was to investigate the utility of measuring urinary leukotriene E4 (LTE4) levels in the diagnosis of atopic diseases in early childhood.

Methods

Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Urinary LTE4 levels were measured and its association between total serum IgE levels, allergen-specific IgE sensitization and atopic diseases were assessed.

Results

A total of 182 children were regular followed up at clinics for a four-year follow-up period. Urinary LTE4 levels appeared to be elevated in children with total serum IgE levels exceeding 100 kU/L, allergen-specific IgE sensitization after 2 years of age. Elevation of urinary LTE4 levels (≥500 pg/mg of creatinine) significantly discriminated high serum total IgE levels (≥100 kU/L) at age 2 (P = 0.027). A higher level of total serum IgE or urinary LTE4 was significantly associated with the risk of developing allergic rhinitis and asthma at age 3. A significantly higher urinary LTE4 level was found in children with a combination of IgE sensitization and asthma at age 4.

Conclusions

Urinary LTE4 levels appear to be highly associated with IgE sensitization and its related allergic airway diseases after age 2. The measurement of urinary LTE4 (≥500 pg/mg of creatinine) could not only be a non-invasive method for atopic predisposition but also potentially provide a strategy for the diagnosis and management of asthma in preschool children.  相似文献   

6.
Background. ABSTExperimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. Materials and Methods. The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. Results. In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). Conclusions. Intestinal parasitic infections and serum IgE levels showed an age‐dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence.  相似文献   

7.

Background

Atopic diseases, including allergic rhinitis, allergic dermatitis and asthma, are common diseases with a prevalence of 30–40% worldwide and are thus of great global public health importance. Allergic inflammation may influence the immunity against infections, so atopic individuals could be susceptible to respiratory infections. No previous population-based study has addressed the relation between atopy and respiratory infections in adulthood. We assessed the relation between atopic disease, specific IgE antibodies and the occurrence of upper and lower respiratory infections in the past 12 months among working-aged adults.

Methods and Findings

A population-based cross-sectional study of 1008 atopic and non-atopic adults 21–63 years old was conducted. Information on atopic diseases, allergy tests and respiratory infections was collected by a questionnaire. Specific IgE antibodies to common aeroallergens were measured in serum. Adults with atopic disease had a significantly increased risk of lower respiratory tract infections (LRTI; including acute bronchitis and pneumonia) with an adjusted risk ratio (RR) 2.24 (95% confidence interval [CI] 1.43, 3.52) and upper respiratory tract infections (URTI; including common cold, sinusitis, tonsillitis, and otitis media) with an adjusted RR 1.55 (1.14, 2.10). The risk of LRTIs increased with increasing level of specific IgE (linear trend P = 0.059).

Conclusions

This study provides new evidence that working-aged adults with atopic disease experience significantly more LRTIs and URTIs than non-atopics. The occurrence of respiratory infections increased with increasing levels of specific IgE antibodies to common aeroallergens, showing a dose-response pattern with LRTIs. From the clinical point of view it is important to recognize that those with atopies are a risk group for respiratory infections, including more severe LRTIs.  相似文献   

8.
Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (T(H)2) cytokine-dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we find that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum IgE concentrations, increased steady-state circulating basophil populations and exaggerated basophil-mediated T(H)2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell-intrinsic expression of myeloid differentiation factor 88 (MyD88) was required to limit serum IgE concentrations and circulating basophil populations in mice. Commensal-derived signals were found to influence basophil development by limiting proliferation of bone marrow-resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal-derived signals influence basophil hematopoiesis and susceptibility to T(H)2 cytokine-dependent inflammation and allergic disease.  相似文献   

9.
BACKGROUND: The association of allergic diseases, drug adverse reactions and elevated total immunoglobulin E (IgE) concentration in systemic lupus erythematosus patients remains controversial. The aim of the study was to investigate the prevalence of those features in active and inactive systemic lupus erythematosus patients, and in the control group as well. METHODS: Total IgE concentration was evaluated by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSIONS: The results of our study revealed that concomitant allergic diseases were not more frequent in systemic lupus erythematosus patients than in the general population. Total IgE concentration was significantly higher during the active stage of the disease. Drug reactions were very frequent but not connected with IgE elevation. Our results indicate that IgE may play a role in lupus pathogenesis, especially in the active phase of the disease.  相似文献   

10.
Anaphylaxis represents an extreme form of allergic reaction. This acute-phase component of allergy and asthma is triggered by allergen-induced degranulation of mast cells following the cross-linking of cell surface-bound, allergen-specific IgE, resulting in the liberation of inflammatory mediators and the development of bronchoconstriction. We used IL-13 transgenic mice to investigate the role of this Th2 cell-derived cytokine in the onset of allergic disease. Strikingly, IL-13-transgenic mice were highly predisposed to fatal anaphylaxis following Ag sensitization. This response correlated with substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also induced phenotypic changes typical of asthma, including pulmonary fibrosis, goblet cell hyperplasia, elevated Th2 cytokines, eosinophilia, and airways occluded by mucus and Charcot-Leyden crystals. Expression of IL-4 was not required for the induction of IgE-mediated responses. These data represent the first characterization of a functional role for IL-13-induced IgE in the generation of immediate hypersensitivity reactions and highlight the importance of IL-13 in the development of the symptoms of atopy. The systemic regulation of this response makes these mice an important resource for studying atopic responses.  相似文献   

11.
High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 x 10(-20) and 7.08 x 10(-19) in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 x 10(-4) and P = 1.95 x 10(-3)). The "top" SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 x 10(-7)-4.46 x 10(-8)) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.  相似文献   

12.
The coincidence between infections with parasitic worms and the reduced prevalence of allergic disease in humans and in animal models has prompted the search for helminth molecules with antiallergic and antiinflammatory potential. We report herein that filarial cystatin, a secreted protease inhibitor of filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic disease in a murine model of OVA-induced allergic airway responsiveness. Treatment with recombinant filarial cystatin inhibited eosinophil recruitment, reduced levels of OVA-specific and total IgE, down-regulated IL-4 production, and suppressed allergic airway hyperreactivity when applied during or after sensitization and before challenge with the allergen. Depletion of macrophages by clodronate-containing liposomes prevented the curative effects and restored the levels of infiltrating cells, IgE, and allergic airway reactivity. Blocking of IL-10 by application of anti-IL-10 receptor Abs restored the reduced number of infiltrating cells and the levels of OVA-specific IgE. In contrast, depletion of regulatory T cells by anti-CD25 Abs had only limited effects. Cystatin also modulated macrophage-mediated inflammation in a murine model of dextran sulfate sodium-induced colitis, leading to reduction of inflammatory infiltrations and epithelial damage. Our data demonstrate that treatment with a single helminth protein can exert the antiallergic effects of helminth infections.  相似文献   

13.
Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD) are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN-gamma and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN-gamma were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls (P<.001). There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 (P = .227). A statistically significant relationship between SCORAD values and serum levels of total IgE (P < .001), IL-18 (P < .001), and IL-12/p40 (P < .001) was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.  相似文献   

14.
Allergy represents a hypersensitivity disease that affects >25% of the population in industrialized countries. The underlying type I allergic immune reaction occurs in predisposed atopic individuals in response to otherwise harmless Ags (i.e., allergens) and is characterized by the production of allergen-specific IgE, an allergen-specific T cell response, and the release of biologically active mediators such as histamine from mast cells and basophils. Regimens permanently tolerizing an allergic immune response still need to be developed. We therefore retrovirally transduced murine hematopoietic stem cells to express the major grass pollen allergen Phl p 5 on their cell membrane. Transplantation of these genetically modified hematopoietic stem cells led to durable multilineage molecular chimerism and permanent immunological tolerance toward the introduced allergen at the B cell, T cell, and effector cell levels. Notably, Phl p 5-specific serum IgE and IgG remained undetectable, and T cell nonresponsiveness persisted throughout follow-up (40 wk). Besides, mediator release was specifically absent in in vitro and in vivo assays. B cell, T cell, and effector cell responses to an unrelated control allergen (Bet v 1) were unperturbed, demonstrating specificity of this tolerance protocol. We thus describe a novel cell-based strategy for the prevention of allergy.  相似文献   

15.
Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen. In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated. In conditions such as Hypereosinophilic Syndrome (HES) circulating eosinophil levels are even further raised. Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear. The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP). This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions. Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis. ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions. ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections. The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil.  相似文献   

16.
Wang M  Xing ZM  Lu C  Ma YX  Yu DL  Yan Z  Wang SW  Yu LS 《Human genetics》2003,113(5):387-390
Allergic rhinitis is a major public health problem and has seen its prevalence increase during the past few decades. Interleukin 13 (IL-13) has been implicated in the pathogenesis and in the regulation of immunoglobulin E (IgE) production. Single nucleotide polymorphisms (SNPs) have been found in both the coding sequence and the promoter region of IL-13, and such SNPs have been associated with allergic asthma. We have investigated whether IL-13 SNPs are associated with allergic rhinitis. Among 188 Chinese adult patients with allergic rhinitis and 87 normal controls, no significant difference was found in either allele or haplotype frequency of the SNPs between the two groups. Within patients, there was a significant association of the IL-13 Arg130Gln SNP, but not of the IL-13 promoter –1112(C/T) SNP, with serum total IgE levels. Patients with a Gln/Gln genotype showed much higher serum total IgE than those with an Arg/Arg genotype. When tested for serum-specific IgE, patients allergic to Derp 1, but not those allergic to Artemisia pollen, showed a significant association with the IL-13 promoter SNP. Thus, our results suggest a possible involvement of IL-13 SNPs in the regulation of IgE production in response to allergens in this Chinese population.M. Wang and Z.-M. Xing should be considered as equal first authors  相似文献   

17.
WBN/Kob-Ht rats (Ht-rats) raised under conventional conditions spontaneously developed dermatitis. In this study, we carried out histopathological analysis to elucidate the pathological features of the dermatitis in Ht-rats. We then tried to detect Staphylococcus species recovered from the skin lesions of Ht-rats. We also measured the serum levels of total IgE, IL-4 and IFN-gamma in these rats. The histopathological data indicated that inflammatory cells had infiltrated the skin lesions. Staphylococcus aureus was recovered from the skin lesions, and the serum levels of total IgE and IL-4 were elevated in Ht-rats with dermatitis. These results suggest that dermatitis in Ht-rats is similar to that in the DS-Nh mice, which has recently been proposed as an animal model for human atopic dermatitis.  相似文献   

18.

Background

Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are common allergic diseases. Environmental factors were indicated to influence the development of allergic diseases.

Objective

To evaluate the correlation between the month of birth and the prevalence of allergic diseases in Taiwan.

Methods

Data from 104,455 children were collected from the National Insurance Research Database of Taiwan. Subjects were identified by at least two service claims for ambulatory care or one claim for inpatient care. All of the enrolled patients were aged 7∼15 years in 2010. In a bio-clinical data analysis, total immunoglobulin E (IgE) and ImmunoCAP™ allergen data (CAP) from mothers and infants were collected in a medical center in Taiwan. Correlations between children''s allergic factors and the season of birth were assessed.

Results

A significant difference in the prevalence of BA according to the month of birth (Χ2 = 18.2, p<0.001) was found in the Taiwanese population. The fewest schoolchildren with were born in May (7.21%), and the most were born in October (10.59%). However, no tendency for the prevalence of AD (Χ2 = 4.6, P = 0.204) or AR (Χ2 = 4.3 P = 0.229) was found. In addition, we found that children born in autumn (August to October) had a higher prevalence of BA compared to those born in spring (February to April) (odds ratio: 1.13; 95% confidence interval: 1.05∼1.21). In a bio-clinical data study, markers of maternal and childhood allergies including IgE and CAP were detected in a risk analysis section. Children who were born in autumn had higher levels of CAP and total IgE.

Conclusions

The findings of this study showed that the month of birth was closely correlated with the prevalence of BA and higher levels of CAP and IgE.  相似文献   

19.

Background

Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools.

Methodology

Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry.

Results

Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease.

Conclusion

Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the clinical evidence of sunflower allergy. Further purification and recombinant expression of these allergens will improve component-resolved diagnosis and therapy of pollen allergy.  相似文献   

20.
Among 67 French patients presenting a toxocaral infection, various demographic, environmental, clinical and laboratory parameters (blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE, specific IgE against common inhalant allergens, specific IgE and IgG4 against Toxocara excretory-secretory antigens) were investigated. Correlation studies and logistic regression analyses were conducted, testing elevated levels of ECP, specific anti-Toxocara IgE or IgG4 as outcome variables An elevated ECP level was significantly associated with both cough and rhinitis, a high level of specific anti-Toxocara IgE with itchy rashes and possible atopic status, and an increase of specific anti-Toxocara IgG4 with rural residence.  相似文献   

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