Elevated Serum Immunoglobulin E Levels Research Articles

Assessment of the Relationship between Adverse Allergic Transfusion Reaction and Serum IgE Level

Background: Allergic transfusion reactions (ATRs) are common adverse events during blood transfusions, ranging from mild urticaria to severe anaphylactic shock. Elevated serum immunoglobulin E (IgE) levels are known to mediate these reactions. This study aimed to assess the relationship between serum IgE levels and the Presence of ATRs in patients receiving fresh frozen plasma (FFP) transfusions. Methods: A cross-sectional observational study was conducted at the Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from March 2019 to August 2021. The study included 55 patients aged 5-60 years who received FFP transfusions. Demographic data, clinical symptoms, and IgE levels were recorded. Data were analyzed using SPSS version 26, with statistical significance set at p<0.05. Result: The majority of participants were males (94.55%) and aged 11-20 years (45.45%). Most patients (85.45%) received multiple units of FFP. Clinical symptoms included itching (56.36%), urticarial rash (29.09%), vomiting (7.27%), and hypotension (7.27%). Raised IgE levels were found in 52.73% of participants, and a significant association was observed between elevated IgE levels and the presence of allergic reactions (p<0.01). Patients with allergic reactions had significantly higher mean IgE levels (521.4±434.6 IU/mL) compared to those without allergic reactions (67.8±33.2 IU/mL). Conclusion: Elevated serum IgE levels are significantly associated with the Presence of ATRs in patients receiving FFP transfusions. Monitoring IgE levels can help predict and manage allergic reactions, thereby improving transfusion safety and patient outcomes.

Ameliorative potential of galangin in murine model of ovalbumin-induced allergic rhinitis: a role of PI3K-PKB pathway.

To examine the potential of galangin in a mouse model of ovalbumin (OVA)-induced allergic rhinitis (AR), as chronic AR, induced by immunoglobulin-E (IgE), leads to histamine release and nasal inflammation, and although galangin exhibits antiasthmatic and anti-inflammatory potential, its effect on AR is yet to be investigated. 126 BALB/c mice. AR induction involved sensitizing female mice with OVA (5%, 500 µL, IP) for 14 days. Post OVA challenge, the mice were divided into 7 groups (n = 18/group), including normal, AR control, montelukast (10 mg/kg), galangin (5, 10, and 20 mg/kg), and per se (galangin [20 mg/kg] treatment. Various outcomes were evaluated, including nasal symptoms, histopathology, biochemistry, and nasal lavage fluid inflammatory cytokines and signaling pathways in nasal mucosal to assess galangin potential in AR. In AR mice, galangin (10 and 20 mg/kg) significantly (P < .05) reduced sneezing, rubbing, and nasal discharge post-OVA challenge. Galangin treatment attenuated (P < .05) elevated serum histamine, β-hexosaminidase, IgE, and Immunoglobulin G1 levels in AR control mice. Additionally, galangin significantly (P < .05) decreased OVA-induced alterations in IL-4, IL-6, IL-13, and interferon-γ levels in nasal lavage fluid compared to AR control mice. Western blot analysis demonstrated that galangin lowered OVA-induced AR by significantly (P < .05) downregulating the phosphorylated protein kinase B and mammalian target of rapamycin-protein expressions while markedly (P < .05) upregulating the glycogen synthase kinase-3β protein expressions in nasal mucosal. Galangin also significantly ameliorated (P < .05) the OVA-induced histological aberrations in the nasal mucosa, reflected by reduced eosinophil infiltration, hyperplasia, and edema. Galangin exhibits antihistaminic and anti-inflammatory effects in AR mice by regulating IgE-mediated histamine and inflammatory release and modulating the phosphatidylinositol 3-kinase/Ak strain transforming/mammalian target of rapamycin pathways.

Elevated IgE Levels-An Allergy or an Underlying Inborn Error of Immunity in Children with Recurrent Infections?

Elevated immunoglobulin E (IgE) is a hallmark of allergic diseases. However, high IgE levels also occur in a number of other infectious and noninfectious diseases. In most cases, elevated IgE levels indicate allergy, eczema, or chronic skin infection. Very high IgE levels are not uncommon in patients with active eczema but more often indicate monogenic atopic disorder or inborn errors of immunity with an atopic phenotype. We conducted a retrospective study of 385 children with suspected immune deficiency referred to the clinic over a 9-year period. Measurement of IgE, IgG, IgA, IgM, and IgG subclasses in blood samples revealed that nearly one-third of the patients had elevated serum IgE levels. Most of the cases with elevated IgE were children with underlying atopy-mainly atopic dermatitis and, to a lesser extent, bronchial asthma-whereas 40.12% (37 children) had no atopy at all. In the most severe cases (with extremely elevated IgE or severe dermatitis), we confirmed genetic mutations for underlying immunodeficiency. Our results indicate that allergic phenotype should not be underestimated and that children with more severe allergic disease should be evaluated for an underlying inborn error of immunity. If inborn error of immunity (IEI) is suspected, a comprehensive immunologic evaluation is required. Genetic testing helps identify the specific genetic abnormality, which provides important insight into the immunopathogenesis of the disease and accurate determination of optimal therapy.

Clinical Images: Giant mass on the forehead in Kimura disease.

The patient, a 68-year-old Asian man with a history of nephrotic syndrome, presented to our department with multiple subcutaneous masses that developed over the past 50 years. The masses were painless, soft, and predominantly located in the head. The mass on the forehead was dome-shaped and had a diameter of 7 cm and a height of 3 cm (A). Blood tests showed eosinophilia and elevated immunoglobulin E (IgE) levels. Serum immunoglobulin G4 levels were normal. Ultrasonography showed heterogeneous masses with marked associated internal hyperemia (B). Magnetic resonance imaging showed T1-weighted isointense and T2-weighted hyperintense masses. A needle biopsy of the forehead mass showed stromal fibrosis, multiple lymphoid follicles, and infiltration of inflammatory cells, mainly eosinophils and lymphocytes. The patient was diagnosed with Kimura disease (KD). The masses shrank rapidly after administration of 30 mg/day of prednisolone for 2 weeks. KD is a rare chronic inflammatory disorder mainly affecting young Asian men. It presents as subcutaneous masses, typically in the head and neck, and is associated with eosinophilia and elevated IgE levels (1). It often affects the cervical lymph nodes and salivary glands (1). It is often associated with renal involvement, such as nephrotic syndrome (2). Glucocorticoids, surgical excision, and radiation therapy are the treatments of choice (3). The diagnosis of KD can be difficult because of its rarity. KD should be considered as a differential diagnosis when patients present with painless subcutaneous masses in the head and neck region with eosinophilia and elevated serum IgE levels.

Elevated Serum Immunoglobulin E Levels are Associated with the Severity of Newly Diagnosed, Acute Vogt–Koyanagi–Harada Disease

ABSTRACT Objective To investigate the correlation between serum immunoglobulin E (IgE) levels and severity of Vogt–Koyanagi–Harada (VKH) disease. Methods The medical records of patients with VKH disease between 2015 and 2020 were reviewed. Serum immunoglobulins (IgA, IgE, IgG, and IgM), tumor necrosis factor α (TNFα) and C-reactive protein (CRP) were measured. Patients were divided into IgE-positive (IgE ≥ 100 IU/mL) and IgE-negative (IgE < 100 IU/mL) groups. The best-corrected visual acuity (BCVA) and macular morphologic characteristics including foveal thickness (FT), serous retinal detachment (SRD), sensory retinal thickness (SRT), central foveal thickness (CFT), cube volume (V), and cube average thickness (AT) were determined in patients in both groups. Results Of 128 patients included in the study, 35 (27.34%) patients were IgE-positive, BCVA (logMAR) was worse in the IgE-positive group. The mean CRP (P= .012) and TNFα (P≤ 0.001) levels were greater in the IgE-positive group than in the IgE-negative group. Regarding macular morphologic characteristics, FT (P= .010), SDR (P= .004), CFT (P= .008), V (P= .013), and AT (P= .006) were significantly greater in the IgE-positive group than in the IgE-negative group. Conclusions Elevated serum IgE levels were associated with more severe macular changes in patients with VKH disease. These findings suggest that IgE may be involved in the progression of VKH disease.

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

BackgroundLow circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable.Methods and findingsWe aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90–1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69–1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92–1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was −0.40 (95% CI −1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia.ConclusionsIn this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.

Fractional exhaled nitric oxide along with a reduced force expiratory volume are conclusive prognostic biomarkers to alert for asthma exacerbation

Background: Asthma is a multidimensional disease with noticeable heterogeneity in its presentation and reaction to treatment. Noninvasive biomarkers to determine disease progression are highly desirable. This study sought to identify fractional exhaled nitric oxide (FeNO), FeNO as a prognostic biomarker for asthma exacerbations, as well as a predictive biomarker for change in other known asthma indicators. Materials and Methods: A prospective, longitudinal study was conducted with a cohort of adult patients with severe asthma who required daily treatment with inhaled corticosteroids. Patients underwent lung function testing using spirometry, sputum samples were taken for inflammatory cell count, and sputum supernatant and exhaled respiration were taken for FeNO, FeNO measurement. Forced expiratory volume levels were measured, along with immunoglobulin E (IgE), eosinophil count, asthma-specific health-related quality of life, asthma-exact signs scores, and time to treatment failure. These indicators were measured over the 22-week study period. Results: A total of 1800 participants were recruited, 56.7% were female, and 70% of the participants were aged 18–27 years. FeNO was valuable prognostic biomarker for asthma exacerbations, along with forced expiratory volume in 1 s reduction. A greater quantity of eosinophils was correlated with a reduced risk of exacerbation in females, with no correlation in males. Elevated serum IgE levels were correlated with an increased risk of lung fibrosis. We found no significant relationships between the investigated indicators and hospitalization. Conclusion: FeNO, in conjunction with other biomarkers, is a useful prognostic indicator of exacerbations of symptoms in asthma patients.

Role of serum immunoglobulin E in patients with interstitial cystitis/bladder pain syndrome

ObjectiveThe actual pathophysiology of interstitial cystitis (IC)/bladder pain syndrome (BPS) is still uncertain. Immune or hypersensitivity mechanisms may play an important role in the pathogenesis of IC/BPS. This study was designed to investigate and analyze serum immunoglobulin E (IgE) levels in patients with IC/BPS. Materials and methodsPatients with IC/BPS who were admitted for cystoscopic hydrodistention were enrolled in this study. Blood samples were obtained to investigate their serum IgE levels. A serum IgE level more than 200 IU/mL was considered abnormal. The patients' symptoms, visual analog scale (VAS) scores, O'Leary–Sant symptom (OSS) scores, cystometric bladder capacity (CBC), maximal bladder capacity (MBC), and grading of bladder glomerulation hemorrhage during cystoscopic hydrodistention were recorded. Serum IgE levels were also investigated in women with stress urinary incontinence, who served as the control group. ResultsTwo hundred patients with IC/BPS and 35 controls were investigated. In total, 22 IC/BPS patients (11%) had abnormal serum IgE levels. No abnormal serum IgE levels were detected in the controls. The mean serum IgE level in IC/BPS patients and controls were 102.37 IU/mL±250.68 IU/mL and 74.21 IU/mL±88.62 IU/mL, respectively (p = 0.204). The VAS, OSS, CBC, MBC, and grading of glomerulations were not significantly correlated with serum IgE levels (p = 0.317, 0.587, 0.774, 0.559, and 0.309, respectively). The serum IgE levels were slightly higher in men than in women, although the difference was not significant (152.98 IU/mL ± 201.73 IU/mL vs. 94.87 IU/mL±262.54 IU/mL, p = 0.183). ConclusionIn this study, 11% of patients with IC/BPS had IgE level more than 200 IU/mL, but the mean serum IgE level was not higher than the controls. Aggravating factors such as food or environmental substance should be carefully investigated in IC/BPS patients with elevated serum IgE levels.

Allergic diseases, immunoglobulin E, and autoimmune pancreatitis: a retrospective study of 22 patients

Background Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of pancreas. We evaluated the clinical manifestations, imaging, and histological presentations of AIP in Chinese patients, and investigated the roles of immunoglobulin E (IgE) and allergic diseases in the diagnosis and pathogenesis of AIP. Methods The clinical records of 22 patients diagnosed with AIP were reviewed and analyzed. All patients with AIP fulfilled the 2006 revised diagnostic criteria proposed by Japan Pancreas Society or the Korean Criteria for AIP. Results Half (11/22) of AIP patients had allergic diseases. Twenty-one patients had elevated serum IgE levels, and 14 patients had IgE levels more than 3 times that of normal. There were no significant differences between the patients with higher or lower IgE, with or without allergic disease, in clinical features, laboratory tests, diffuse or focal lesions, or the choice of treatment methods; however, more complaints of body weight loss were observed in patients with higher IgE levels. Patients with higher IgE levels and with allergic diseases were more likely to have onset in March, April, May, August, September, or October. IgE levels decreased after therapy, but increased again during recurrence. Increased number of mast cells was found in the pancreatic tissue in AIP. Conclusions IgE maybe a useful marker for monitoring therapeutic response and recurrence of AIP. Allergic processes may play an important role in the pathogenesis of AIP.

Kimura’s disease or IgG4-related disease? A case-based review

Kimura's disease usually presents with benign painless soft tissue swelling around the head and neck areas with eosinophilia and high immunoglobulin E (IgE) levels. IgG4-related disease is characterized by fibrosis and sclerosis of the involved organs, with infiltration of IgG4-positive plasma cells. There are some similar clinical manifestations of these two diseases, with eosinophilia or high IgE levels often found in patients with IgG4-related disease. However, the relation between these two diseases is not well known. We report a 23-year-old man who had multiple neck lumps for longer than 1 year. He had remarkable eosinophilia and elevated serum IgE levels. Biopsy of his lymph nodes suggested the diagnosis of both Kimura's disease and IgG4-related disease. In this article, we discuss the relationship between Kimura's disease and IgG4-related disease. We also suggest a possible model ("allergen-specific immunotherapy") to illustrate our view that an increase in IgG4-positive plasma cells is an epiphenomenon of Kimura's disease.

Understanding the genetic regulation of IgE production

Immunoglobulin E (IgE) is a key mediator of anti-parasitic and anti-tumour immunity. However it is also a critical component of atopic and autoimmune diseases, and elevated serum IgE levels are a common indicator of immune dysregulation. In this review we survey the literature on genetic associations of elevated IgE in humans and mice. We find that defects in a limited number of pathways explain the majority of gene associations with IgE. Commonly, elevated IgE is associated with defects in Th bias and B cell class switching, severe T cell tolerance defects and defects in immunity at the host–environment interface. These genetic data demonstrate the mechanisms of control over IgE production and the manner in which they can be circumvented.

Bambusae Caulis in Taeniam extract reduces ovalbumin-induced airway inflammation and T helper 2 responses in mice

Ethnopharmacological relevance Bambusae Caulis in Taeniam (BC) was known as traditional herbal medicine with anti-inflammatory property in the Orient. Aim of the study Allergic asthma is inflammatory disease of airways associated with enhanced T helper (Th) 2 lymphocytes responses to allergens, leading to eosinophilic infiltration and elevated serum IgE levels. Although there were some studies that BC extract had an anti-inflammatory property, there was no study on asthma. In present study, we investigated the suitability of BC extract as a therapeutic candidate in the treatment of allergic airway disease in ovalbumin-induced asthma model. Materials and methods Balb/C mice (female, 6 weeks old) were treated by ovalbumin sensitization and nebulization, and used as asthma model. The number of eosinophil in bronchoalveolar lavage (BAL) fluid and the degree of eosinophila were investigated by hematoxylin and eosin stain and the infiltration of inflammatory cells into lung tissues was examined by staining by hematoxylin and eosin solution. The levels of interleukin (IL)-4 in BAL fluid, immunoglobulin E (IgE) in serum, interferon (IFN)-γ and IL-4 production in splenocyte culture from Balb/C mice (not treated, 6 weeks old) that incubated with or without BC extract for 48 h were determined by enzyme-linked immunosorbent assay. Results The level of eosinophils was decreased by treatment of the animals with BC extract (40 mg/kg) and correspondingly, a significantly lowered degree of eosinophila was also reported ( p < 0.01). In lung tissue, BC extract reduced the increased immune cell infiltration induced by OVA ( p < 0.05). Furthermore, the levels of IL-4 and IgE in BAL fluid or serum up-regulated by OVA was decreased by BC extract. Finally, IFN-γ production was significantly increased ( p < 0.01), while IL-4 production significantly decreased ( p < 0.01), after treatment of the culture supernatants of splenocytes with BC extract. Conclusions These results indicated that BC extract reduces OVA-induced airway inflammation and Th 2 response in mice, suggesting that BC extract can be a therapeutic candidate for allergic airway disease, including asthma.

Elevated serum immunoglobulin E (IgE): When to suspect hyper-IgE syndrome—A 10-year pediatric tertiary care center experience

Elevated serum immunoglobulin E(IgE) can be caused by allergies, infections and immune conditions including hyper IgE syndrome (HIES). HIES is a rare primary immunodeficiency disease most commonly characterized by a triad of findings, including increased serum IgE levels, recurrent skin abscesses, and pneumonias leading to pneumatocele formation. The objective of this study was to characterize the clinical profile of patients presenting with increased IgE levels (>or=2000 IU/mL) focusing specifically on HIES. A database search identified 70 patients in the pediatric age range (<or=18 yrs.) between January 1997 and December 2006 who had an IgE level of >or=2000 IU/mL. Charts were abstracted for clinical diagnosis, comorbidities, and laboratory parameters. Data were analyzed using the students t-test, Wilcoxon signed rank test, and univariate/multivariate regression models. Clinical diagnosis in 70 patients with elevated IgE levels were: atopic diseases (n = 54; 77%), parasitic diseases (n = 1; 1.5%), malignancy (n = 2; 3%), and HIES (n = 6; 8%), among other causes. There was a statistically significant association between IgE levels and the severity of eczema (p = 0.009). Ninety percent of the subjects with IgE level >or=2000 IU/mL did not have HIES. There was no correlation between IgE levels and the diagnosis of HIES (p = 0.5). A variety of clinical situations result in an elevated IgE level, with atopy being the most common cause. In the absence of typical clinical features, elevated serum IgE levels are not predictive of HIES.

Hypogammaglobulinaemia secondary to cow‐milk allergy in children under 2 years of age

Symptomatic hypogammaglobulinaemia in children younger than 2 years of age was studied to rule out a primary immunodeficiency. Thirty-four patients were referred to the Immunology Service to study the hypogammaglobulinaemia-associated clinical picture. Food allergy was documented in 10 patients by personal and familial history, presence of specific immunoglobulin E (IgE) and elevated total serum IgE levels. Coeliac disease and human immunodeficiency virus infection were also ruled out. Protein loss through stools was assessed by clearance of alpha1-antitrypsin (AAT). Serum immunoglobulin levels were determined by nephelometry and functional antibodies were studied by enzyme-linked immunosorbent assay. The cellular immune response was assessed by in vitro lymphocyte proliferation in response to mitogens and cell subsets were analysed by flow cytometry. In five patients of the 10 patients we suspected a protein loss through the mucosa. Four of these five patients showed an increased AAT and the other showed an extensive cutaneous lesion. Immunological studies revealed normal antibody function, in vitro lymphoproliferative responses and cell numbers in four of the 5 patients. One patient showed abnormally low numbers of CD4(+) T cells as well as a defective proliferative response to mitogens. After diagnosis of cow milk allergy, milk was replaced with infant milk formula containing hydrolysed proteins. Recovery of immunoglobulin values and clinical resolution were achieved. Hypogammaglobulinaemia during early childhood in some children may be secondary to cow milk allergy, and immunoglobulins and cells may leak through the inflamed mucosa. Resolution of symptoms as well as normalization of immunoglobulin values may be easily achieved by avoidance of the offending allergen.

IgE and atopy in perinatally HIV‐infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.

Atopic dermatitis or hyper-IgE syndrome?

A case of atopic dermatitis (AD), recurrent infections, and elevated immunoglobulin E (IgE) level is presented. Clinical characteristics, pathophysiology, diagnosis, and management in this patient are reviewed. Clinical pearls and pitfalls include the following: (1) deep-seeded Staphylococcus aureus infections occur rarely in AD and should raise the possibility of immunodeficiency syndromes such as hyper-IgE syndrome (HIES); (2) HIES is characterized by a clinical triad consisting of elevated serum IgE levels, recurrent staphylococcal skin abscesses, and pneumonia with pneumatocele formation; (3) although serum IgE levels in AD have been noted to be as high as 10,000 IU/mL, severe cases of AD such as that presented here can exceed this range; (4) the efficacy of anti-IgE therapy in AD or HIES is unknown and may be limited by dosing requirements.

Gene-Gene Interaction in Asthma: IL4RA and IL13 in a Dutch Population with Asthma

Asthma is a common respiratory disease that is characterized by variable airways obstruction caused by acute and chronic bronchial inflammation; associated phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum immunoglobulin E (IgE) levels, and skin tests positive to common allergens. Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure. These cytokines also share a common receptor component, IL4R alpha. We have investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch families ascertained through a proband with asthma. By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction between S478P in IL4RA and the -1111 promoter variation in IL13, previously shown to be associated with BHR (P=.003), was detected. Individuals with the risk genotype for both genes were at almost five times greater risk for the development of asthma compared to individuals with both non-risk genotypes (P=.0004). These data suggest that variations in IL4RA contribute to elevated total serum IgE levels, and interaction between IL4RA and IL13 markedly increases an individual's susceptibility to asthma.

Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype.

The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor prognosis and is often correlated with faster CD4(+) cell depletion and rapid disease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV-1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 -589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected individuals, especially in those at advanced stages of disease. In contrast, neither a triallele polymorphism in IL-10, another Th2 cytokine, nor a biallele polymorphism in the RANTES promoter affected acquisition of the SI phenotype. This finding suggested that IL-4-589T increases IL-4 production in the human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.

Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD.

Bronchodilator responsiveness has been associated with a subsequent accelerated decline in forced expiratory volume in one second (FEV1). Therefore, bronchodilator responsiveness and total serum immunoglobulin E(IgE) levels were assessed in 184 adult first-degree relatives of probands with severe early-onset chronic obstructive pulmonary disease (COPD) and a control group. Greater bronchodilator responsiveness was found among current smokers or exsmokers who were first-degree relatives of early-onset COPD probands than in currently or exsmoking controls, expressed as increase in FEV1 as a percentage of baseline (5.8+/-8.1 versus 2.9+/-5.1%, p<0.01), absolute increase in FEV1 from baseline (120+/-130 versus 60+/-110 mL, p<0.05), and increase in FEV1 as a percentage of the predicted value (3.6:4.1 versus 2.2+/-3.9%, p<0.05). However, elevated total serum IgE levels were not found in first-degree relatives of early-onset COPD probands compared with control subjects. The increased bronchodilator responsiveness among currently smoking/exsmoking first-degree relatives of early-onset COPD probands suggests that these individuals may have enhanced susceptibility to the detrimental effects of cigarette smoking.

Damp Housing and Childhood Respiratory Symptoms: The Role of Sensitization to Dust Mites and Molds

In 1990, a case-control study was conducted in the Netherlands into the association between damp housing, childhood respiratory symptoms, and sensitization to house dust mites and mold allergens. In this study, 259 children with chronic respiratory symptoms and 257 control children were involved. Total serum immunoglobulin E (IgE) and specific IgE against house dust mites and a mixture of molds were determined. A visual inspection for signs of home dampness was performed in all homes. A questionnaire was given to the parents of the children to elicit information about the presence of signs of dampness in the previous 2 years and about risk factors for childhood respiratory disease. In the case group, 94 children had elevated serum IgE levels to house dust mites and 24 children to the mixture of molds. In the control group, house dust mite allergy was found in 31 children and mold allergy in two children. In a crude analysis, cases were slightly more likely to have been living in homes where damp or mold was reported or observed than were the controls. In cases as well as controls, home dampness was associated with increased sensitization to dust mites and molds. There was no relation between home dampness and case-control status after stratification for sensitization, however. Restriction of the analysis to cases with elevated serum IgE levels against dust mites and/or molds, and to controls without elevated serum IgE, increased the odds ratios, and several became significant at p < 0.05. This supports a connection between damp housing and sensitization to dust mites and/or molds and childhood respiratory symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)