Characterization of polyclonal allergen-specific IgE responses by affinity distributions

Polyclonal IgE responses have been previously characterized by allergen-specific antibody levels and by identification of amino acid sequences related to immunodominant epitopes. However, the binding affinities related to these antibody families are not well known. Using sera from donors with known sensitivities to ragweed or house dust mite allergens, we studied the binding reactions between the purified allergens Amb a 1 and Der p 1 and allergen-specific IgE's by determining affinity distribution functions. The distributions of binding affinities only exhibited a few dominant reactions indicated by peaks in an affinity distribution display. In all the donors tested, there were two dominant peaks and in 2/3 of the cases there was a third peak for both Amb a 1 and Der p 1. We further characterized the polyclonal interactions between IgE and Der p 1 by inhibiting the specific binding of IgE using peptide fragments known to be constituents of Der p 1 epitopes. Each peptide inhibited only a single peak in the affinity distributions. It would appear that the peaks in the affinity distribution represent antibodies directed to single epitopes. These results suggest that in our atopic population the response is surprisingly uniform. The bulk of the IgE response (70-80%) is of high affinity (10(8)-10(11) M(-1)) and directed towards a few epitopes. The relative affinities towards epitopes seem to be determined by the structure of the epitope and not variations of individuals' immune responses.     

Head circumference at birth and maternal factors related to cord blood total IgE

BACKGROUND: A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. OBJECTIVES: To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. METHODS: Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. RESULTS: In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm, respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). CONCLUSIONS: Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.     

Hydrocortisone enhances allergen-specific IgE production by peripheral blood mononuclear cells from atopic patients with high serum allergen-specific IgE levels.

BACKGROUND: Although there is convincing evidence that human B cells can be induced to produce IgE by a combination of interleukin 4 (IL-4) and hydrocortisone (HC) in atopic subjects, it is still uncertain if this performs the same functions in allergen-specific IgE synthesis. OBJECTIVE: This study was designed to investigate the differences of IgE regulation between atopics and nonatopics, interactions of HC with IL-4, and the correlation between in vitro total IgE, allergen-specific IgE synthesis and serum IgE levels. METHODS: Peripheral blood mononuclear cells (PBMCs) from 16 atopic asthma patients sensitive to Dermatophagoides farinae and seven nonatopic controls were cultured with IL-4 and/or HC. Total IgE and D. farinae-specific IgE in culture supernatant were measured by ELISA and FAST. RESULTS: IL-4 increased total IgE synthesis in PBMCs from both atopics and nonatopics, whereas, HC had this effect only in some atopics who showed spontaneous IgE production in vitro. HC acted synergistically with IL-4 in total IgE synthesis. Their effects were more remarkable in cases with lower total serum IgE levels. PBMCs from eight of 16 atopics produced D. farinae-specific IgE in vitro either spontaneously or by IL-4 and/or HC. HC had more profound effects than IL-4 in these patients. They also showed higher total IgE synthesis by HC, and higher specific serum IgE levels than the others. IL-4 and/or HC did not induce any D. farinae-specific IgE synthesis by PBMCs from nonatopics. CONCLUSION: HC had a more profound effect than IL-4 on the induction of D. farinae-specific IgE synthesis in atopic patients with high serum allergen specific IgE levels. Further studies to determine the causes of these effects, such as the presence of long lived allergen specific B cells as the result of the priming effect of IL-4 in vivo, may be needed.     

Effects of maternal allergen-specific IgG in cord blood on early postnatal development of allergen-specific T-cell immunity

BACKGROUND: A wide body of epidemiologic evidence indicates that as yet unknown maternal factor(s) can influence susceptibility to allergic disease in the offspring. It is also well established that the induction of allergen-specific T-cell memory is frequently initiated in utero, and it is likely that maternal factors exert their influence during this period. METHODS: This study examines the relationship between maternally derived allergen-specific IgG subclass antibodies and cellular immune responses (lymphoproliferation and cytokine production) against the same allergens in 49 subjects tested at birth and at 2 years of age. Polyclonal production of the Th1 cytokine IFN-gamma was also examined in the cord-blood samples. RESULTS: At birth, there were positive correlations between both house-dust mite (HDM)- and ovalbumin (OVA)-specific IgG subclass levels in cord blood, maternal atopy, and the magnitude of perinatal lymphoproliferative responses to respective allergens. Inverse relationships were also observed between cord-blood IgG antibody titres and allergen-specific production of some Th2 cytokines. However, there were no consistent relationships between cord-blood allergen-specific IgG antibodies and subsequent immune responses to allergens when the same subjects were retested at 2 years of age. An inverse relationship was observed between maternal history of atopy and perinatal IFN-gamma production capacity. CONCLUSIONS: Our results suggest that transplacental transfer of allergen-specific IgG antibody is unlikely to be a major mechanism for maternal regulation of allergen-specific immunity in infancy. An alternative possibility is that maternal effects may operate by influencing IFN-gamma production by T cells in the offspring.     

Experimental studies on red cell-based assays for total IgE and allergen-specific IgE

The potential of red cell-based assays for IgE and allergen-specific IgE has been examined using mouse monoclonal anti-human IgE antibodies and chimaeric human IgE anti-4-hydroxy-3-iodo-5-nitrophenacetyl. Experiments concerned with developing a red cell IgE antibody-capture assay for allergen-specific IgE have pointed to the advantages of presenting the allergen on a second agglutinable red cell.     

Effects of winter birth season and prenatal cockroach and mouse allergen exposure on indoor allergen-specific cord blood mononuclear cell proliferation and cytokine production

BACKGROUND: Season of birth has been associated with the development of atopy and asthma. Relationships among a particular birth season, maternal allergen exposure during the birth season, and childhood development of allergies to allergens in higher concentration during the birth season may be important. OBJECTIVE: To investigate the effects of winter birth (January 1 to March 31) and prenatal cockroach and mouse allergens in settled dust on indoor allergen-specific cord blood mononuclear cell (CBMC) proliferation, TH2 production, and cord blood IgE concentration. METHODS: As part of an ongoing prospective study, 350 cord blood samples were collected. The CBMCs were cultured with cockroach, dust mite, and mouse protein extracts, and proliferation was measured. Interleukin 5, interferon-delta, and total IgE levels were measured. Home dust samples were analyzed for cockroach and mouse allergens. RESULTS: An isolated association was observed between winter birth and a greater mean (SD) cockroach interleukin 5 ratio (winter vs nonwinter birth: 26,043 [11,403] vs 11,344 [3,701]; P = .02). Other associations between winter birth and increased CBMC proliferation, T-helper cytokines, or cord blood IgE levels were not detected. Higher mouse allergen levels were associated with decreased mouse-induced proliferation (winter vs nonwinter birth: mean [SD] stimulation index, 1.72 [0.12] vs 2.02 [0.11]; P = .04). CONCLUSIONS: Winter birth and increased cockroach or mouse allergen levels during pregnancy were not consistently associated with greater CBMC proliferation, T-helper cytokine production, or cord blood IgE levels. Greater indoor allergen exposure during pregnancy does not seem to affect the development of cockroach or mouse immune responses in utero.     

Longitudinal trends of total and allergen-specific IgE throughout childhood

Background:  The development and the quantitative relationship between allergen-specific IgE (S-IgE) responses and total IgE (T-IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S-IgE and T-IgE during childhood.
Methods:  We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age ( n  = 273) and at 1, 3, 5, 6, 7, 10 and 13 years ( n  = 84). Total-IgE and the overall level of specific-IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino-conjunctivitis and asthma were ascertained by questionnaires.
Results:  Longitudinal patterns of T-IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log₁₀) transformed values of T-IgE and of S-IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T-IgE vs a constantly increasing trend of T-IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age.
Conclusions:  Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S-IgE levels. Therefore, variations in T-IgE levels at school age closely reflect variations in overall S-IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.     

Low-affinity receptor for IgE on human bronchial epithelial cells in asthma.

Bronchial epithelial cells are activated in asthma but the mechanisms underlying this activation are poorly understood. We tested the possibility that bronchial epithelial cells recovered by brushing from 15 asthmatic and 11 control subjects may be activated by an IgE-dependent mechanism. The expression of the low-affinity IgE receptor (CD23) was studied by immunocytochemistry using the alkaline phosphatase anti-alkaline phosphatase technique and immunofluorescence using confocal microscopy. Four of eight allergic asthmatic patients and none of the seven non-allergic asthmatic or control subjects had a positive expression of CD23. The functional activity of CD23 was examined in the cells recovered from these subjects by stimulating them with IgE/anti-IgE. 15-HETE was not released but endothelin was released in the three or four asthmatic patients who had a positive expression of CD23. None of the other subjects released any endothelin. This study suggests that bronchial epithelial cells of asthmatic patients may be directly activated by an IgE-mediated mechanism.     

Clustering of fungal allergen-specific IgE antibody responses in allergic subjects

Statistical analysis of specific IgE immune responses to a panel of nine allergens from 2,094 patients demonstrated significant clustering between Aspergillus fumigatus, Alternaria alternata, and Cladosporium herbarum, not explained by crossreactive elements. This may represent a linked, high responder status to these fungal antigens in the allergic population.     

武汉市1996-1997年围产儿出生缺陷监测结果分析

从1996年4月开始在武汉市46家设有产科的医院开展围产儿出生缺陷监测。监测对象为在监测医院分娩的妊娠28周以上围产儿,监测结果表明,武汉市出生缺陷发生率为4.94‰,低于全国及全省的发生率水平;出生缺陷发生明显性别差异。产母年龄以及出生季节对出生缺陷的发生亦无显著影响;从出生缺陷发生的种类来看,唇、腭裂发生高居首位,神经管畸形致死率最高,并提出孕早期监护对预防出一缺陷的发生具有重要意义。     

Parental history of atopic disease and concentration of cord blood IgE

Background A family history of atopy, and cord blood immunoglobulin E concentration, have been shown to be predictors of atopic disease in children. Several studies have suggested that parental atopy may be related to newborn immunoglobulin E. Objective The purpose of our analysis was to evaluate whether parental history of allergic disease was associated with cord blood immunoglobulin E concentration. Methods The study subjects were from a defined population of 777 newborns delivered between 1987 and 1989. The mothers of these children completed a questionnaire during pregnancy concerning themselves and the child's father, including parental history of physician diagnosis of allergic diseases (allergies, hay fever and asthma). Total immunoglobulin E levels were quantitated in cord blood samples with an enzyme-hnked immunoassay. Results Median cord blood immunoglobulin E concentration was higher among infants whose mothers had a history of atopic disease, particularly for those with a history of asthma (P<0.022) and allergen immunotherapy (P<0.016) vs infants whose mothers had no history of any atopic disease. Comparing all babies with a maternal history of asthma, to babies where neither parent had a history of any atopic disease, the median cord blood immunoglobulin E was significantly higher (0.36IU/mL vs 0.21 IU/mL; P<0.009). This association was found only among female infants (0.49IU/mL vs 0.20 IU/mL; P<0.001). Conclusion Maternal, but not paternal, history of atopic disease was associated with an elevated immunoglobulin E among newborns. For maternal asthma, this association was only evident in infant girls.     

The role of allergen-specific IgE,IgG and IgA in allergic disease

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen-specific IgE then binds to the high (FcεRI) and low-affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen-presenting cells. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell–mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared with IgE and do not efficiently interfere with allergen-induced inflammation. However, IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mast cells and basophils. Here, we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.     

The relationship of allergen-specific IgE levels and oral food challenge outcome

BACKGROUND: Oral food challenges remain the gold standard for the diagnosis of food allergy. However, clear clinical and laboratory guidelines have not been firmly established to determine when oral challenges should be performed. OBJECTIVE: We sought to determine the value of food-specific IgE levels in predicting challenge outcome. METHODS: A retrospective chart review of 604 food challenges in 391 children was performed. All children had food-specific IgE levels measured by means of CAP-RAST before challenge. Data were analyzed to determine the relationship between food-specific IgE levels and challenge outcome, as well as the relationship between other clinical parameters and challenge outcome. RESULTS: Forty-five percent of milk challenges were passed compared with 57% for egg, 59% for peanut, 67% for wheat, and 72% for soy. Specific IgE levels were higher among patients who failed challenges than among those who passed (P 相似文献   

Functional evaluation of the basophil/IgE system in the cord blood

Basophil releasability was studied in 24 cord blood samples from normal-term deliveries. The histamine content in cord blood basophils was similar to that of adult blood basophils. The response to IgE-independent degranulating stimuli such as calcium ionophore A23187 and zymosan-activated human serum was overlapping with that of normal adults. Conversely, a reduced releasability was observed after challenge with anti-IgE, even after sensitization with an IgE-rich serum. The IgE-dependent degranulation seems to be hampered by the low concentrations of circulating and cell-bound IgE antibodies. The number of IgE molecules bound to the specific receptors in cord blood basophils is significantly lower than in adult blood basophils.