IgE elevation temporally associated with dermal Glufosinate ammonium exposure in an elderly patient: A case report from Vietnam

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To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.

Asymptomatic lymphoma associated with elevation of immunoglobulin E.

Most children and adults living in areas where the endemicity of Plasmodium falciparum malaria is high have significantly elevated levels of both total immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. This elevation is highest in patients with cerebral malaria, suggesting a pathogenic role for this immunoglobulin isotype. In this study, we show that IgE elevation may also be seen in severe malaria without cerebral involvement and parallels an elevation of tumor necrosis factor alpha (TNF). IgE-containing serum from malaria immune donors was added to tissue culture plates coated with rabbit anti-human IgE antibodies or with P. falciparum antigen. IgE-anti-IgE complexes as well as antigen-binding IgE antibodies induced TNF release from peripheral blood mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevation induced significantly less of this cytokine, and the TNF-inducing capacity of malaria sera was also strongly reduced by passing them over anti-IgE Sepharose columns. The cells giving rise to TNF were adherent PBMC. The release of this cytokine probably reflects cross-linking of their low-affinity receptors for IgE (CD23) by IgE-containing immune complexes known to give rise to monocyte activation via the NO transduction pathway. In line with this, adherent monocytic cells exposed to IgE complexes displayed increased expression of CD23. As the malaria sera contained IgG anti-IgE antibodies, such complexes probably also play a role in the induction of TNF in vivo. Overproduction of TNF is considered a major pathogenic mechanism responsible for fever and tissue lesions in P. falciparum malaria. This overproduction is generally assumed to reflect a direct stimulation of effector cells by certain parasite-derived toxins. Our results suggest that IgE elevation constitutes yet another important mechanism involved in excessive TNF induction in this disease.

Rationale:Extreme elevation of serum immunoglobulin E (IgE) concentration is a key marker for detecting immune disorders, including humoral and cellular defects in primary immunodeficiency (PID). IgE antibodies are present in low concentrations in the body and are produced in large amounts when exposed to infections or toxins. However, IgE is also the cause of allergic symptoms and life-threatening anaphylaxis reactions. Early diagnosis of PID associated with elevated IgE may lead to effective or life-saving therapeutic interventions. Therefore, genomic testing-based diagnosis is becoming a widely used diagnostic tool to determine the cause of disease.Patient concerns:Three Vietnamese patients with increased IgE expression were collected for genetic analysis at The Allergy, Immunology, and Rheumatology Department, Vietnam National Hospital Pediatrics.Diagnoses:Primary immunodeficiency associated with elevated IgE.Interventions:We performed whole-exome sequencing (WES) to detect novel associated variants and confirmed these by Sanger sequencing. The effects of the variants were predicted using in silico prediction tools.Outcomes:Three novel pathogenic variants including c.2204A > T, p.Asp735Val in the PTPRC gene, c.586T > A, p.Phe196Ile in the UNC119 gene, and c.481C > T, p.Arg161Cys in the IL21R gene were found to be associated with increased IgE.Lessons:We report novel variants associated with genetic defects that increase IgE found in PID patients. These results emphasize the need for accurate diagnosis and appropriate intervention to improve outcomes and quality of care for individuals with high IgE levels and related immune disorders.

Perivascular Mast Cells Dynamically Probe Cutaneous Blood Vessels to Capture Immunoglobulin E

BackgroundPolycyclic aromatic hydrocarbons (PAHs) have become common pollutants with industrial development. Although the effect of exposure to PAHs on allergic disease in humans has been evaluated, evidence of an association is sparse. The association between PAH exposure and serum total immunoglobulin E (IgE) levels was evaluated in Korean adults.MethodsIn total, this study included 3,269 participants in the Third Korean National Environmental Health Survey (2015–2017). Four urinary PAH metabolites were used to assessed exposure to PAHs: 1-hydroxypyrene, 1-hydroxyphenanthrene, 2-naphthol, and 2-hydroxyfluorene. The analyses were performed on 3 cutoff levels (100 IU/mL, 114 IU/mL, and 150 IU/mL) set as the total IgE elevation. Prevalence of total IgE elevation by PAH exposure group and general characteristics (age, sex, BMI, smoking, alcohol drinking, and occupation) were analyzed using the Rao–Scott χ2 test. Multiple logistic regression analyses were conducted to calculate adjusted odds ratios (ORs) for total IgE elevation by PAH exposure groups.ResultsTotal IgE elevation differed significantly by age, sex, smoking status, alcohol drinking status, and occupation. For 2-hydroxyfluorene, the fourth quartile showed a significant association with IgE elevation compared to the first quartile in the analyses of cutoff-level 100 IU/mL (OR: 1.372, 95% confidence interval [CI]: 1.007–1.869) and 114 IU/mL (OR: 1.643, 95% CI: 1.167–2.312). In the analysis of cutoff-level 150 IU/mL, the adjusted ORs of the third and fourth quartile of 2-hydroxyfluorene were significantly higher than the first quartile (3rd quartile: OR: 1.478, 95% CI: 1.034–2.113; 4th quartile: OR: 1.715, 95% CI: 1.161–2.534). However, there were no significant positive associations for the other metabolites.ConclusionsThis study implied that PAHs exposure is associated with total IgE elevation in Korean adults. More research is needed to confirm the effect of exposure to PAHs on serum IgE and allergic diseases.

BackgroundIt has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa.MethodsForty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo).ResultsIndividuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production.ConclusionThe findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-499) contains supplementary material, which is available to authorized users.

T Cell Epitope-Specific Defects in the Immune Response to Cat Allergen in Patients with Atopic Dermatitis

Background: Allergen sensitization is a risk factor for the development of bronchial asthma in adults. However, the relationship between allergen sensitization and lung function in asthma patients is not well understood. This study was conducted to evaluate the relationship between sensitized allergens, total serum immunoglobulin E (IgE) level, and lung function in adult asthmatic patients in northern Taiwan.Methods: A total of 266 adult Taiwanese patients diagnosed with asthma between January 2003 and December 2004 were enrolled. Age, sex, duration of asthma, pulmonary function tests, total IgE, eosinophilic cationic protein, and specific IgE of ImmunoCAP were recorded. Allergic was defined as the presence of a specific IgE to 1 or more allergens.Results: There were 161 (60.5%) male and 105 (39.5%) female patients, with a mean age of 60.46 ± 15.40 years. The mean duration of asthma was 13.64 ± 7.35 years. Mite allergens, Dermatophagoides pteronyssinus (48.46%) and Dermatophagoides farina (49.23%), were the most common indoor allergens. We divided the patients into allergic and nonallergic asthma groups: 164 (61.7%) patients had allergic asthma and 102 (38.3%), nonallergic asthma. Patients with allergic asthma were younger, and had a higher total IgE level and better lung function than the nonallergic asthmatics (p＜0.05, respectively). Total serum IgE was correlated to peak expiratory flow (PEF) variability (r=0.3395, p＜0.0001) in asthmatic patients. Among allergic asthmatics, the serum total IgE and PEF variability were higher as the number of positive allergen-specific IgE tests increased.Conclusions: Defining asthma phenotypes as allergic or nonallergic is essential. This study supports the difference between allergic and nonallergic asthma. Patients with allergic asthma were younger and had higher total IgE and better lung function than patients with nonallergic asthma.

Background: Asthma is a life-threatening immediate-type allergic disease. B cell-activating factor (BAFF) is a key regulator of B lymphocyte development and is required to generate and maintain the mature B cell pool. Objectives: To investigate the level of BAFF in the serum of asthma patients and the role of BAFF on T cells. Methods: The BAFF level was measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMC) from asthma patients were analyzed by flow cytometry. T8.1 cells were used to test the role of BAFF on T cell-antigen-presenting cell (APC) conjugate formation. Results: The BAFF level in patient serum was elevated relative to normal serum. Immunoglobulin E (IgE) concentration and the percentage of CD3+ T and CD19+ B cells vary according to the serum BAFF level. Patients with high BAFF and high IgE (group II) and those with high BAFF and low IgE (group III) show a high ratio of CD3+ T to CD19+ B cells, and the opposite is seen for patients with low BAFF and high IgE (group I) and those with low BAFF and low IgE (group IV). The addition of BAFF increased PBMC proliferation and T cell-APC conjugate formation. BAFF concentration in serum decreased after treatment with antiasthmatic drugs including glucocorticoids and immunosuppressants. Conclusion: These findings suggest that the serum BAFF level is high in both IgE-mediated asthma and non-IgE-mediated asthma and extend our knowledge about the fact that BAFF may play a stimulatory role on the proliferation of T cells. Thus, BAFF could be a parameter to monitor the severity of asthma symptoms.

BackgroundThe prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine–phosphate–guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort.MethodsAtopy was assessed via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort. After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1. The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex. Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464).ResultsIn stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E−9 to 1.4E−5) and 12 associated with high IgE levels (P-value range 1.1E−5 to 7.1E−4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available sites, 13 were replicated.ConclusionsWe identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5′UTR of PRG2, cg27469152 in the 3′UTR of EPX, and cg09332506 in the body of COPA).Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0213-8) contains supplementary material, which is available to authorized users.

BackgroundThe benefit of probiotics in newborn children in relation to allergy and general morbidity later in life appears to be controversial. Allergic diseases represent an increasingly important health problem worldwide in recent years. This is evident in all age groups. The occurrence of allergic illnesses also continues to rise exponentially, and thus the use of preventive and prognostic methods, particularly in children with an inherently higher risk of allergy, is gaining increased importance.Since the advent of probiotics the effect of probiosis on immunity through alterations of composition and function of the human gut microbiome has been increasingly studied. The exact mechanisms have not yet been clearly defined.The Academy of Sciences of the Czech Republic (The Czech Academy of Sciences has suggested that the expression of TH1 and TH2 cytokines in umbilical blood is associated with an increased risk of allergies. The counter -balance of Th1 and Th2 affect Immunoglobulin E (IgE) production and maturation of the gastrointestinal tract epithelium.Case presentationWe examined IgE levels in 3000 samples of umbilical blood taken from children born into families with a positive history of allergy in one or both parents from 2007 to 2017.At the age of ten days, those with high IgE were given Colinfant Newborn (a lyophilized non-pathogenic strain of Escherichia.coli) for one month, three times weekly. At 15 months and three years we investigated the levels of Immunoglobulins E,A and G, and the incidence of illness and allergy.The results revealed that allergy and high umbilical IgE is strongly linked with family history (p ≤ 0.001). We also detected differences in seasonality, especially with regards to pollen allergies. Eighty percent of children treated with Colinfant Newborn had significantly reduced IgE and morbidity at 13–15 months and 3 years, and furthermore without any clinical signs of allergy. Normalization of Immunoglobulins A and G was seen in 90% of treated subjects (p ≤ 0.001). These levels significantly correlated with an almost negligible morbidity up to 4 years of life.Colinfant Newborn, a lyophilized strain of Esherichia coli (E. coli), and a normal component of intestinal flora, readily colonizes the intestinal tract. It’s long term presence significantly stimulates the production of specific and non-specific intestinal antibodies. and optimalizes immune development through tolerance. In our study Colinfant Newborn reduced the incidence of infections later in life by safely and effectively normalizing immunoglobulin levels in the majority of treated patients.ConclusionOur study strongly suggests as positive effect of physiological Escherichia coli on the microbiome of newborn children as evidenced by a significantly reduced incidence of allergy and morbidity when applied early in life. These benefits appear to be strongly strain specific.

Humanized Monoclonal Antibodies Against IgE Antibodies as Therapy for IgE-Mediated Coronary Syndromes: Are We There Yet?

Analysis of reproductive toxicity and classification of glufosinate-ammonium