Changes In IgE Levels Research Articles

A meta-analysis investigating the efficacy and safety of allergen-specific immunotherapy in the management of respiratory allergies

Background This meta-analysis aimed to evaluate the effectiveness and adverse effects of specific immunotherapy (SIT) in the management of respiratory allergens, including allergic asthma, rhinitis, and related disorders, based on a review of current literature up to November 8, 2022. Methods We conducted a search of databases, including PubMed, Embase, Cochrane, and Web of Science, to identify relevant randomized controlled trials (RCTs) assessing respiratory allergy-specific immunotherapy. We employed the Consolidated Standards of Reporting Trials (CONSORT) Statement to select RCTs that adhered to rigorous reporting standards. Specifically, we focused on double-blind placebo-controlled (DBPC) trials and open studies involving both adults and children, considering factors such as dosage, inclusion criteria, allergens, and primary outcome measurements. Results A total of 25 meta-analyses were included in this study. Among them, 14 evaluated sublingual-specific allergen immunotherapy (SLIT), 4 assessed subcutaneous allergen immunotherapy (SCIT), 4 explored both sublingual and subcutaneous immunotherapy, and 3 investigated intralymphatic immunotherapy. The outcomes of these meta-analyses indicated a reduction in medication scores in 20 cases and a decrease in symptom scores in 23 cases. Additionally, six studies reported on changes in IgE levels, seven studies focused on IgG4, four studies examined FEV1 (forced expiratory volume in 1 s), and eight studies reported on symptom and medication scores. Furthermore, 11 studies reported on differences in adverse reactions. Conclusion The results of our meta-analysis suggest that specific immunotherapy, while associated with some adverse effects, effectively reduces the symptoms of asthma and rhinitis. Therefore, we recommend its use in the treatment of respiratory allergies.

Correlation Between a Deficiency of D3 Levels and the Development of Allergic Rhinitis.

&lt;b&gt;Background and Objective:&lt;/b&gt; Allergic rhinitis (AR) is a common disorder characterized by sneezing, runny nose, nasal congestion and lacrimation, which negatively affects the quality of life to a large extent. The study aimed to find a link between the effect of vitamin D3 levels on Immunoglobulin (IgE) levels in patients with allergic AR. &lt;b&gt;Materials and Methods:&lt;/b&gt; This study included 30 patients with AR, with ages ranging from 18 to 35, of both sexes. For vitamin D levels, &lt;u&gt;>&lt;/u&gt;30 ng/mL is considered sufficient and &lt;u&gt;<&lt;/u&gt;20 ng/mL is a deficiency. The second group includes 30 people with adequate levels of vitamin D3 as a control group. All results were analyzed statistically by ANOVA, in addition to using the regression coefficient test to test the extent of the effect of D3 on the development of allergic rhinitis at a significant level of p&lt;u&gt;<&lt;/u&gt;0.05 using the SPSS program 24. &lt;b&gt;Results:&lt;/b&gt; The results showed a significant decrease in the levels of vitamin D3 in the serum of the AR patients compared with the control group and a substantial increase in the levels of IgE in the serum of the AR patients compared with the control group at a significant level of p&lt;u&gt;<&lt;/u&gt;0.05. Additionally, the results showed in the regression coefficient an inverse and significant effect of vitamin D3 concentration on serum IgE levels, which is significant in terms of the p-value, which appeared equal to 0.010. By observing the value of the R&lt;sup&gt;2&lt;/sup&gt; coefficient of determination, it is clear that a change in the concentration of vitamin D3 causes 58% of the changes in IgE levels. &lt;b&gt;Conclusion:&lt;/b&gt; Through linear regression correlation, an inverse linear relationship emerged linking low vitamin D3 levels to increased IgE levels with an effect rate of 58%.

Real-Life Data on the Use of Omalizumab in Patients with Severe Asthma and Chronic Urticaria and Mepolizumab in Patients with Severe Asthma: A Retrospective Study

This study aimed to assess the real-life effectiveness of omalizumab and mepolizumab in patients with severe asthma and chronic spontaneous urticaria (CSU), explicitly examining changes in IgE levels and eosinophil counts during treatment. This retrospective study involved patients with severe asthma or CSU treated with biologic agents, including omalizumab and mepolizumab. The primary outcome measures were serum IgE levels, eosinophil counts, urticaria activity scores (UAS), and asthma control test scores (ACT). We studied 61 patients with severe asthma or chronic urticaria treated with biological agents. Patients with asthma exhibited a significant reduction in the median annual attack rate from 4 to 0 with omalizumab (p&amp;lt;0.001) and from 6 to 1 with mepolizumab (p&amp;lt;0.001). Eosinophil counts, and ACT scores significantly decreased with mepolizumab (p&amp;lt;0.001). Six patients who transitioned from omalizumab to mepolizumab did not experience severe asthma attacks in the first six months following the treatment switch. Patients with CSU showed a significant response to omalizumab (p&amp;lt;0.001). We observed significant improvements in various markers, including total IgE levels, eosinophil counts, UAS, and ACT scores, indicating that these treatments can effectively manage the symptoms of both conditions. These findings underscore the potential benefits of using these treatments as effective therapeutic options.

FFA2 Activation Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice.

Gut microbiota produce dietary metabolites such as short-chain fatty acids, which exhibit anti-inflammatory effects. Free fatty acid receptor 2 (FFA2, formerly known as GPR43) is a specific receptor for short-chain fatty acids, such as acetate that regulates inflammatory responses. However, the therapeutic potential of FFA2 agonists for treatment of atopic dermatitis has not been investigated. We investigated the efficacy of the FFA2 agonist, 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), for treatment of atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Long-term application of DNCB to the ears of mice resulted in significantly increased IgE in the serum, and induced atopic dermatitis-like skin lesions, characterized by mast cell accumulation and skin tissue hypertrophy. Treatment with 4-CMTB (10 mg/kg, i.p.) significantly suppressed DNCB-induced changes in IgE levels, ear skin hypertrophy, and mast cell accumulation. Treatment with 4-CMTB reduced DNCB-induced increases in Th2 cytokine (IL-4 and IL-13) levels in the ears, but did not alter Th1 or Th17 cytokine (IFN-γ and IL-17) levels. Furthermore, 4-CMTB blocked DNCB-induced lymph node enlargement. In conclusion, activation of FFA2 ameliorated DNCB-induced atopic dermatitis, which suggested that FFA2 is a therapeutic target for atopic dermatitis.

No genetic association detected with mepolizumab efficacy in severe asthma.

Treatment with mepolizumab, a humanized monoclonal antibody to interleukin-5, reduces the rate of asthma exacerbations and the requirement for systemic glucocorticoids while maintaining asthma control. Treatment decisions are guided by predictors of response, including blood eosinophil thresholds in patients with frequent exacerbations despite intensive anti-inflammatory and controller treatment. Identification of additional predictors of response could aid treatment decisions. We investigated genetic associations that may predict response to mepolizumab-treatment. In this post hoc analysis of DREAM and MENSA, association of genetic markers was tested in patients with severe asthma treated with mepolizumab who provided consent for pharmacogenetic research. Association was tested in a tiered approach with alpha spend differing for candidate genetic markers selected for prior history of association with relevant traits or pathways and in a genome-wide analyses (p<4.7×10-4 and p<5×10-8, respectively). Efficacy endpoints included: clinically significant exacerbation rate (tested using a negative binomial model), time to first exacerbation (tested with a Cox proportional hazards model), change in exacerbation rate, change in eosinophil count, and change in IgE level (tested by linear regression). No genetic marker was significantly associated with the primary endpoint, clinically significant exacerbation rate. One genetic marker was associated with time to first clinically significant exacerbation, but this association was driven by the DREAM data and was not supported in additional sensitivity analyses by treatment regimen/dose. No genetic effect on mepolizumab-treatment response was identified in this population on intensive asthma treatment, with history of frequent exacerbations and pre-selected for airway eosinophilia.

Influence of Omalizumab on Allergen-Specific IgE in Patients with Adult Asthma

Background: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). Methods: tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. Results: Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against Dermatophagoides pteronyssinus, crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), Candida (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. Conclusions: The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.

Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations

Physicians have questioned whether omalizumab can be discontinued or the dose reduced after clinical improvement is seen in patients with severe asthma. To examine the relationships among omalizumab, free IgE, and clinical outcomes in a randomized, placebo-controlled trial in patients with severe persistent allergic asthma following a posology based on pretreatment total IgE and body weight. A pharmacokinetic-pharmacodynamic binding model was used to calculate free IgE, omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up of the INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) study. These were plotted against the mean changes in the total asthma symptom score, morning peak expiratory flow, and rescue medication use for physician-defined treatment responders and nonresponders. The model accurately fitted omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function. Omalizumab and free IgE correlated well with clinical symptoms. Reducing omalizumab doses below those in the dosing table cannot be recommended; the resulting increase in free IgE would cause a deterioration in asthma control.

Combined Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo

Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-gamma promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-gamma promoter and hypomethylation of IL-4 in CD4+ T cells among mice sensitized to the fungus allergen Aspergillus fumigatus. We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4+ cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-gamma promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG(-45), CpG(-53), CpG(-205) sites of the IFN-gamma promoter and hypomethylation at CpG(-408) of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis.

Omalizumab rapidly decreases nasal allergic response and FcεRI on basophils

Background Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. Objective This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcεRI receptors on basophils. Methods We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD 30 ragweed nasal allergen challenge, patients received either omalizumab, ∼0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD 30 dose biweekly. FcεRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. Results Mean IgE levels decreased by 96% ( P < .001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days ( P < .001) and 12.2% at 35 to 42 days ( P < .001) for the omalizumab group. There was a median decrease in basophil FcεRI expression of 73% ( P < .001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcεRI expression were observed throughout the study in the placebo group. Conclusions Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcεRI receptor expression on immune effector cells.

Attenuation of allergic airway inflammation and associated pulmonary functions by mycobacterial antigens is independent of IgE in a mouse model of asthma

Since the observation that Bacillus Calmette–Guérin (BCG) vaccination in children correlates with a decreased prevalence of asthma, several investigators have been attempting to reproduce this effect experimentally in mouse models of asthma. While these reports have agreed in some areas, uncertainty has remained as to the effect of BCG on IgE and asthmatic response in general. Furthermore, the effect of mycobacterial antigens on the early allergic response and the release of bronchoconstrictory mediators have not been examined. In the present study, we have aimed to more completely describe the effect of BCG and Mycobacterium vaccae on early and late allergic responses (EAR and LAR, respectively), airway hyperresponsiveness (AHR) and broncho-constrictory mediators in the mouse model of allergic airway inflammation. Using BALB/c mice sensitized to ovalbumin (OVA) and treated twice with either BCG or M. vaccae (1 × 105 CFU, intranasally), we investigated airway resistance of both the EAR and LAR, AHR to methacholine, serum total and antigen-specific IgE, cysteinyl leukotrienes in bronchoalveolar lavage (BAL) fluid (10 min following challenge), a complete cell differential of the BAL (24 h post-challenge), BAL and serum cytokines and lung histology. Neither BCG nor M. vaccae were able to attenuate the EAR, yet both were able to abrogate the parameters used to evaluate the LAR. Interestingly, in neither case were serum or OVA-specific IgE levels reduced after treatment with mycobacterial antigens and type 1/type 2 T cell cytokine skewing, based on cytokine levels in BAL and serum, was incomplete. These results have led us to conclude that the mycobacterial antigens elicit potential anti-asthmatic effects independent of changes in IgE levels. We speculate that mycobacteria likely directly or indirectly suppress eosinophil effector function via attenuation of type 2 T cell-mediated immune responses.

Monitoring allergen immunotherapy of pollen‐allergic patients: the ratio of allergen‐specific IgG4 to IgG1 correlates with clinical outcome

Although allergen immunotherapy has been established as a treatment of type I allergy back in 1911, until now the underlying mechanisms have not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in the meantime. We wanted to define allergen-specific parameters that change due to treatment in correlation with the clinical outcome. We conducted a controlled study with grass pollen-allergic children and compared allergen-specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy children. Two recombinant forms of the major allergen group V of Phleum pratense (Phl p 5) served as model allergens. No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen-specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amounts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symptom scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics have hardly any measurable allergen-specific IgG antibodies and no IgE antibodies at all. The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment reflects a possible influence of this subclass on the induction of tolerance towards allergens.

HyperImmunoglobulin E Syndrome: Clinical and Immunologic Evaluation within One Family 41

Hyper IgE syndrome (HIE) is characterized by recurrent staphylococcal deep-seated infections, mucocutaneous candidiasis, chronic eczematous dermatitis, bone fractures, and coarse facies. A father and two daughters (now 1 and 5 yrs old) with classical manifestations of HIE provided a unique opportunity for early and sequential evaluation of clinical and immunologic parameters. Extremely high serum IgE may be caused by abnormalities in T lymphocyte function and cytokine production. Measurements of T cell populations and cytokines that control IgE production, IL-4 and IFN-γ, have found variable results in HIE. In this family, IgE levels were 0 - 100 IU/ml in the first year of life, rising to >36000 at 4 yrs in one child. T cell responses to mitogens and antigens were already decreased. In the first year, the absolute CD 4 counts were increased (mean 5670) with normal percentages due to elevated total lymphocyte counts. CD8 counts near the lower limit of normal (mean 600) resulted in elevated CD4:CD8 ratios (range 5 to 11). Naive CD4CD45RA and committed CD4CD45RO showed a normal pattern: CD45RA decreased with age while CD45RO increased. Neutrophil dysfunction, especially in chemotaxis, also is reported in HIE. Assessment of neutrophil receptors showed a significantly decreased expression of the CD11b/CD18 heterodimer at 38%/35% for the younger child and 33%/45% for the older girl. In contrast, neutrophils from their father expressed CD11b/CD18 at normal levels. FcRIII(CD16) expression on neutrophils showed a strikingly different pattern: both children had a dual population of cells. 25-45% of neutrophils had decreased expression at 50% control, but 75-55% of cells had greatly upregulated FcRIII from 3.4 to 67 times normal. The father had a single population of FcRIII at 180% of control. Changes in IgE levels, T lymphocytes, and the expression of neutrophil receptors within this family suggest an age-related pattern. These findings may help in understanding the functional abnormalities, and potentially to identify the genetic defect in this rare primary immunodeficiency syndrome.

SERUM IgE LEVELS IN INFANTS AND ITS CHANGES UP TO OVER 1 YEAR OF AGE

When I proposed the standard values of serum IgE levels in children before, supposed values were used in infants, since serum IgE levels in low range could not be measured at that time. As we were able to determine the IgE value in low range using Pharmacia RIA or LUMIWARD assay system, I tried to evaluate the formerly proposed standard IgE values in infancy.However, the standard values of serum IgE levels in infancy could not be evaluated from the distribution of IgE levels because of the small number of “low IgE infants”. A part of these infants were then monitord for the changes of IgE levels up to over 1 year of age.As the results, the formerly proposed standard IgE values were proved to be appropriate even in infancy.

Atopy in subjects with asthma followed to the age of 28 years

The relationship between markers of asthma and atopy was examined in 323 subjects at the age of 28 years who have been followed since the age of 7 years. Hay fever was common in all groups with severe asthma, increasing from 25% of the control group to 67% of the group with the most severe asthma, class V. Eczema was uncommon at this age in all groups. IgE levels, peripheral blood eosinophil counts, and skin reactions were significantly ( p < 0.05) higher in class V than in the control group. Increasing age was associated with a progressive fall in eosinophil counts and an increase in skin reactivity to common allergens. No change in IgE levels was observed from 21 to 28 years. A general relationship between bronchial hyperreactivity and atopic markers was found. However, only the occurrence of hay fever was significantly related to reactivity when account was taken of severity of asthma. The results indicate that the relationship between asthma and atopy observed at earlier reviews continues into adult life and that bronchial hyperreactivity and atopy are not directly linked.

Colostral transfer of bovine immunoglobulin E and dynamics of serum IgE in calves

The role of IgE in protective immunity is becoming understood, therefore the colostral transfer of IgE and the age-dependent changes of IgE levels may be important for neonatal immunity. To investigate this question, serum samples were collected from range-fed Hereford cows and their calves from birth through 9 months of age. The sera were assayed for total IgE by enzyme-linked immunosorbent assay (ELISA). Calves were found to have significant levels of IgE during the first week postpartum, indicating colostral transfer of IgE. Thereafter, serum levels declined rapidly within 3 weeks from birth. The IgE levels began to increase after 12 weeks of age, and in some cases reached adult levels. The passive transfer of maternal IgE through colostrum may be important in providing early protection from disease, especially against intestinal parasites.

Immunoglobulin E response during viral infections

One hundred and three patients (90 nonatopics and 13 atopics) with respiratory infections to various viral agents were studied retrospectively with respect to IgE immunoglobulin levels during acute (1 to 7 days) and convalescent (8 to 30 days) phases of infection. It was found that 59% of patients had a decrease of 20% or more in IgE level, 27% remained the same, and only 14% showed a rise of 20% or more from the acute to the convalescent phases of infection. IgE levels decreased up to 3 to 4 wk after symptoms and the degree of decrease was more apparent for the nonatopics who had higher IgE levels in their acute phase of infection. Less dramatic decrease in IgE was observed for the 13 atopics studied. The changes in IgE levels during the viral infectious period are discussed in terms of possible cellular mechanisms that may control IgE immunoglobulin.

Atopic dermatitis and IgE. Relationship between changes in IgE levels and severity of disease

At the Mayo Clinic, atopic dermatitis was evaluated in a series of 28 patients to determine whether, during the course of the disease, serum IgE levels fluctuated with changes in the severity of dermatitis. The study covered a 1- to 11/2-year follow-up period. Previously, it had been shown that, at initial examination, serum IgE levels were positively related to the extent of disease. Although notable fluctuations in serum IgE levels and in extent of dermatitis were seen in more than half of the cases, no relationship was found between the two factors during the period of study.