High Total IgE Levels Research Articles

Diagnosis of allergic sensitization in patients with allergic rhinitis and asthma in a tropical environment.

Few studies in tropical developing countries have utilized molecular diagnosis to characterize allergen-specific responses to aeroallergens. To investigate the in vivo and in vitro responses of IgE antibodies to inhalant allergens in allergic patients with rhinitis and/or asthma. A prospective study in which patients with allergic rhinitis and/or asthma were included. Skin prick tests with 16 inhalant extracts of allergens were carried out and total and specific IgE levels for allergens and their molecular components in the serum were determined. In a total of 189 patients, 73.5% showed high levels of total IgE in the serum. The prick tests were positive for the following allergens: Dust mite extracts; more than 60 %, cat; 29.6 %, dog; 23.4 %, and Periplaneta Americana; 21.6 %. Specific IgE for Dermatophagoides farinae and Pteronyssinus was present in 66.6 % of the patients; for Blomia tropicalis; in 45.0 %, for Ascaris lumbricoides; in 24.7 %, for cat; in 17.3 %, for parrot feathers; in 14.8 %, and for Penicillium notatum; in 12.3 %. IgE antibodies to mite allergens of group 1 and 2 were present in 59.0 % and 70.1 % of the sera; 39.1 % contained IgE to rBlo t5, 30.4 %contained rBla g4, 19.9 % contained rFel d1, 11.8 % contained rArt v3, 11.2 % contained Der p10, 9.9 % contained rBla g2, 9.3 % contained rPer a7, 9.3 % contained nFel d2, and 8.7 % contained rCan f1. This study confirms that mites are the main sensitizing agents in patients with respiratory allergic diseases in a tropical environment. There was a good correlation between the results of the skin tests and the results of the in vitro tests.

The hidden impact of different Blastocystis genotypes on C-3 and IgE serum levels: a matter of debate in asthmatic Egyptian children.

Blastocystis hominis is highly prevalent with respiratory allergies among Egyptian children. Yet, little is known about the possible immunological relationship. Aims of this study were to measure complement-3 (C-3), total and specific IgE to intestinal allergens in patients' serum regarding the identified B. hominis genotypes. In a cross-sectional study, three hundred children (150 asthmatics and 150 non asthmatics) participated in the study from both sexes, mean age 7.5 ± SD (3-4) years after a questionnaire administration. PCR-based genotyping of B. hominis selective in vitro cultivation was performed. C-3, total and specific IgE were all measured in patients' serum utilizing ELISA. Blastocystosis was detected in 100 out of 300 children, 65 (43.3%) out of 150 asthmatics and 35 (23.3%) out of 150 non-asthmatics. Vacuolar forms were the most prevalent in both direct wet mount and stool cultures. Forty (61.5%) out 65 asthmatics and 5 (14.2%) out of 35 non-asthmatics were ≥ 5 organisms/HPF. Sex and irritable bowel disease were statistically insignificant (p value < 0.05). Urticaria was coincided in 15.4% of asthmatics and 8.6% of non-asthmatics. Of 100 cases of blastocystosis, eighty-four were genotype-3 and sixteen were genotype-4. Out of these, 55 cases of genotype-3 and 6 cases of genotype-4 were asthmatics. Positive C-3 serum levels were in 46 (54.81%) of genotype-3 and 2 (12.5%) of genotype-4. High total IgE levels in 30 (35.7%) out of 84 cases of genotype-3 and 4 (25%) out of 16 cases of genotype-4. Positive specific IgE was in 25 (29.8%) of genotype-3 and 3 (18.75%) of genotype-4. Genotype-3 was of higher infection intensity (p value = 0.0001). In conclusion, B. hominis possess a hidden allergy triggering impact that can be obscured by simultaneous high (total and specific) IgE levels towards specific common intestinal allergens. Blastocystosis induces allergy by increasing C-3 serum levels in a genotype-dependent manner being higher in genotype-3. Virulence of genotype-3 seems to stand beyond increased parasite intensity and wide absorption of intestinal allergens that indirectly elevate IgE serum levels.

Clinical utility of serum specific IgE food testing in general practice: A tertiary care experience

Serum Specific IgE (SSIgE) testing is the preferred method for diagnosis of food allergy by Primary Care Physicians(PCPs). However, the diagnostic value of such tests, without a valid history, is questionable due to high false positive results. We tested the hypothesis that greater than 50% of positive food allergens according to Serum Specific Immunoassays do not correlate with a definitive food allergy. We performed a medical record review on 336 patients previously diagnosed with “food allergies” based on positive SSIgE ordered by PCPs. We compared these SSIgE results with an assessment from our tertiary care center Allergy specialists which included detailed history, skin prick testing and home/in office oral challenges. The top 10 foods tested by PCPs were milk, peanut, wheat, shrimp, soybean, codfish, walnut, egg, sesame, and scallop. 167 (49.7%) subjects had positive skin testing to one or more foods. Only 41(12.20%) had positive oral food challenges. Average total serum IgE per patient was 581IU/ml (ref: 100-300IU/ml). SSIgE assay was obtained only on 71 subjects in 2008 compared to 240 in 2018. False positive rate in our study is >80 % compared to >50% in the previous studies.A high average total serum IgE level/ patient related to nonspecific IgE and cross-reactive but clinically irrelevant allergen SSIgE might be a reason for false-positive IgE values for the specific food allergen.A rising trend for indiscriminate ordering of SSIgE in the last 10 years has caused not only the over diagnosis of food allergy but also an unnecessary cost of evaluation.

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort

The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P<.001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset.

ASSOCIATION OF MATRIX METALLOPROTEINASES GENE POLYMORPHISM WITH CLINICAL MANIFESTATIONS OF BRONCHIAL ASTHMA IN CHILDREN

In the present study, we have examined association between different polymorphic variants of metalloproteinases genes and clinical manifestations of bronchial asthma in children. We observed 103 patients including 42 children with an established diagnosis of asthma. Moreover, 61 persons were examined in the control group. All patients underwent genetic testing by allele-specific polymerase chain reaction. In particular, 320A&gt;C polymorphic locus of ММР20 gene; Val275Ala ММР20, and -8202A&gt;G gene ММР9 were analyzed.We have found that 30 patients (71.4% of total) had bronchial asthma of mild severity, 9 children (21.4%) exhibited moderate degree, and 3 patients (7%) had severe-grade disease. Homozygous C/C variant of the polymorphic ММР20 gene, 320A&gt;C heterozygous variant of the ММР20 Val275Ala polymorphism, and heterozygous locus of -8202A&gt;G ММР9 gene were found to be most frequent among the children with asthma. Generally, we have observed that the frequencies of the studied alleles and genotypes did not significantly differ berween the asthma patients and children from the control group (p &lt; 0.05). However, in patients with GGgenotype of -8202A&gt;G ММР9 polymorphism combined with homozygosity for the C allele of ММР20 320A&gt;C, a more severe disease was observed, being combined with polyvalent sensitization and high total IgE levels in blood serum.In conclusion, frequencies of alleles and genotypes among patients with asthma did not show any statistically significant differences from the group of healthy children. The patients homozygous for G allele of ММР9 -8202A&gt;G polymorphism gene and for the C allele ММР20 gene (320A&gt;C) seem to be predisposed for a more severe clinical course of the disease.

Pemphigoid nodularis - rare presentation of bullous pemphigoid: A case report and literature review.

Pemphigoid nodularis (PN) is a rare clinical variant of bullous pemphigoid characterized by the presence of nodular prurigo-like lesions and pemphigoid blisters. The diagnosis is confirmed by direct immunofluorescence (DIF)/ indirect immunofluorescence (IIF) and immunoserology tests. For some patients, with long mean duration of symptoms, the correct diagnosis of PN is delayed because the disease is not recognized. We present a case and summarize the reported characteristics of PN. The search in MEDLINE database, after selection, resulted in 36 articles presenting 47 cases of PN. Between published cases a female predominance was noted (female to male ratio of 1.8:1), almost half of the reported patients were non-Caucasian, and the mean age at presentation was 66.2 years. The mean duration until the diagnosis was almost 2 years. Sixteen patients also had other autoimmune diseases. Twenty-two patients developed vesicles/bullae/urticarial plaques before or after the diagnosis. Peripheral eosinophilia and high levels of serum total IgE were reported in 10.6 and 27.2% of patients, respectively. ELISA for either BP180, BP230 or both were positive in all tested cases. DIF and IIF microscopy were positive overall in 100 and 92.3% of cases, respectively. Corticosteroids, either topical or systemic, were the most efficient therapeutic option, although many others were used. PN remains a diagnostic and therapeutic challenge in elderly patients with unexplained refractory chronic pruritus associated with papulo-nodular lesions.

Characterization of tenascin-C as a novel biomarker for asthma: utility of tenascin-C in combination with periostin or immunoglobulin E

BackgroundExtracellular matrix proteins tenascin-C (TNC) and periostin, which were identified as T-helper cell type 2 cytokine-induced genes in human bronchial epithelial cells, accumulate in the airway basement membrane of asthmatic patients. Although serum periostin has been accepted as a type 2 biomarker, serum TNC has not been evaluated as a systemic biomarker in asthma. Therefore, the objective of this study was to evaluate whether serum TNC can serve as a novel biomarker for asthma.MethodsWe evaluated 126 adult patients with mild to severe asthma. Serum TNC, periostin, and total IgE concentrations were quantified using enzyme-linked immunosorbent assays.ResultsSerum TNC levels were significantly higher in patients with severe asthma and high serum total IgE levels. Patients with both high serum TNC (> 37.16 ng/mL) and high serum periostin (> 95 ng/mL) levels (n = 20) or patients with both high serum TNC and high serum total IgE (> 100 IU/mL) levels (n = 36) presented higher disease severity and more severe airflow limitation than patients in other subpopulations.ConclusionsTo our knowledge, this is the first study to show that serum TNC levels in asthmatic patients are associated with clinical features of asthma and that the combination of serum TNC and periostin levels or combination of serum TNC and total IgE levels were more useful for asthma than each single marker, suggesting that serum TNC can serve as a novel biomarker for asthma.

THE C-159T POLYMORPHISM OF THE CD-14 GENE AND CYTOKINE PROFILES IN ADULTS WITH ATOPIC DERMATITIS

Introduction A C-to-T transition has been identified at position 159 in the promoter region of the CD14 gene. This functional single-nucleotide polymorphism C-159T has been associated with high levels of IgE and allergy. Methods The C-159T polymorphism of CD-14 gene was studied in 96 patients with atopic dermatitis. The control group included 90 non-atopic volunteers. The single nucleotide polymorphism of C-159T was detected by PCR. The levels of total IgE and TNF-α, IL-2, Y-IF, IL-4, IL-5, IL-10, TGF-β cytokines in blood were detected by ELISA Patients and volunteers provided written informed consent for the genetic study. Results 34 patients had exogenous and 62 had endogenous atopic dermatitis. In the control group, the frequency distribution of genotypes (CC – 20 (22.2%), CT – 48 (53.3%), TT – 22 (24.5%)) was significantly different from those with atopic dermatitis (CC – 39 (40.6%), CT – 37 (38.5%), TT – 20 (20.9%), X2 = 7.45, p = 0.024). The prevalence of the CC genotype increases the risk (OR=1.798, p=0.043) of exogenous atopic dermatitis development being associated with high levels of total IgE, IL-5 and low IL-10, and TGF-β in blood. The risk of endogenous (OR=0.321, p=0.007) and exogenous (OR=0.484, p=0.045) atopic dermatitis development is decreased in CT and TT genotypes. Conclusions The risk of atopic dermatitis development in this Ukrainian population is increased with the prevalence of allele C and decreased with the allele T of the polymorphic region C-159T of the CD14 receptor.

Camel's milk allergy.

Camel's milk is a safe and therapeutic nutrient. Camel's milk allergy is almost unknown. To identify the clinical and laboratory features of camel's milk allergy. In this retrospective study, the records of patients with camel's milk allergy were reviewed. Data collected included age, sex, clinical presentation, concomitant allergies, family history, laboratory tests (complete blood cell count [CBC], white blood cell [WBC] count, total immunoglobulin E [IgE], food specific IgE), and skin-prick tests (SPT) to camel's milk and other foods. Nine patients (four male patients, five female patients; mean age ± SD 4.3 ± 2.4 years) presented with cutaneous urticaria and/or angioedema (five patients [55.6%]) and anaphylaxis (four patients [44.4%]). Allergic reactions occurred within the first 15 minutes of ingesting camel's milk in all the patients (100%). Concurrent allergies were observed in 77.8% of the patients, of whom, five patients (71.4%) had atopic dermatitis (AD) and two patients (22%) had cow's milk allergy that exacerbated AD. All the patients (100%) had a family history of allergies. The family farm was the source of camel's milk in all the patients (100%). The WBC count was 9425 ± 1452.8 (mean ± SD) cells/μL, and eosinophils was 612 ± 455.4 (mean ± SD) cells/μL, and the median IgE was 301.5 kU/mL. A camel's milk SPT resulted in a wheal of 8.7 ± 4.9 (mean ± SD) mm. Camel's milk allergy is a distinct, yet very rare, disease entity. Cutaneous and systemic allergic reactions are the main clinical manifestations. Concomitant other allergies, viz., AD, and positive family history are risk factors. Early life exposure to camel's milk is a possible risk factor. High blood eosinophil counts and total IgE levels were observed in patients with camel's milk allergy. In the presence of a consistent and specific clear-cut history of camel's milk-related symptoms, a SPT was a dependable confirmatory test.

The J-shape association of serum total IgE levels with age-related cataract.

To address the association between serum total IgE levels and age-related cataract in adults. The study participants consisted of 1052 adults aged 40y or older in the Korean National Health and Nutrition Examination Survey 2010. We performed multivariable logistic regression analyses using the quartile cut-points of total IgE levels. The odds ratios (ORs) for nuclear and any cataract with ≥267 kU/L of serum IgE levels were 1.75 [95% confidence intervals (CI), 1.04-2.96] and 2.00 (95%CI, 1.22-3.27), respectively, comparing to 35-87 kU/L. Interestingly, participants with ≤35 kU/L of IgE levels (OR, 1.67; 95%CI, 1.02-2.72) also had higher risk for any cataract than those with 35-87 kU/L. The risk for any cataract (OR, 1.48; 95%CI, 1.03-2.13) was higher in participants with high total IgE levels (>150 kU/L), comparing to normal participants. Our findings indicate a J-shaped relationship between serum IgE levels and age-related cataract.

Clinical predictors of the effectiveness of tiotropium in adults with symptomatic asthma: a real-life study.

Long-acting muscarinic antagonist (LAMA) tiotropium improved lung function and reduced risks of exacerbation when added on to inhaled corticosteroids (ICS) with or without long-acting B2 agonists (LABAs) in patients with uncontrolled asthma. However, studies predicting the effectiveness of tiotropium based on patients' clinical characteristics were limited. We conducted this retrospective study at a single medical center from July 2016 to July 2017, and used asthma control test (ACT) to evaluate the effectiveness of tiotropium add-on therapy in patients with uncontrolled asthma. The effectiveness was shown by an increase in ACT score from baseline of 3 or greater after 3 months of tiotropium add-on therapy. Patients with uncontrolled asthma despite the use of low- or medium- to high-dose of ICS plus LABA (n=160) were analyzed. Among patients having good response (n=112, ACT score increased ≥3 points) to tiotropium (TGR group) and patients having poor response (n=48, ACT increased <3 points) to tiotropium (TPR group), their baseline characteristics including age, asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), cigarette use, initial FEV1, serum IgE level, eosinophil count, and BMI were significantly different. Univariate analysis showed that old age, ACO, cigarette use, initial FEV1 <80%, and BMI >30 were predictors of the effectiveness of tiotropium. Patients with high serum total IgE level >430 µg/L and eosinophil count >0.6×109/L had a negative impact on response to tiotropium. Multivariate logistic regression analysis demonstrated that the independent factor of poor response to tiotropium was high serum IgE level >430 µg/L. Tiotropium add-on therapy in patients with uncontrolled asthma was effective. However, patients with serum total IgE level >430 µg/L were less likely to benefit from tiotropium.

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.

Targeting IgE Antibodies by Immunoadsorption in Atopic Dermatitis.

One major hallmark of atopic dermatitis (AD) is the elevated level of total serum IgE, which has been reported to be partly of the autoreactive type in a subset of patients. Immunoadsorption (IA) has been successfully applied in various classical autoantibody-mediated diseases such as pemphigus. Recent reports proposed the use of IA also for patients with severe AD and high total serum IgE levels. In this mini-review, we summarize the current knowledge about this novel treatment approach for AD and briefly discuss the so far incompletely known role of autoreactive IgE as potential target of IA therapy in this common inflammatory skin disorder.

Food Allergy in Children with Inherited Epidermolysis Bullosa. The Results of the Observational Study

Background: Inherited epidermolysis bullosa (EB) refers to a group of rare inherited disorders characterized by severe damage of skin and in most patients — the gastrointestinal mucosa, what leads to a violation of skin and mucosal barrier properties in relation to allergens. However, the issues of food sensitization and food allergy in this category of patients have not been studied, and the study of this problem is important.Aim: To evaluate the clinical manifestations of food allergy (FA) and IgE-response to food proteins in children with EB.Methods: 82 patients with EB aged from 2 months to 16 years were entered this open non-randomized observational prospective study, including 20 patients with simple form of EB and 62 patients with dystrophic form of EB. We analyzed allergic history and clinical manifestations of the FA in all the patients. Every patient in this study underwent of determination of the concentration of total serum IgE and specific serum IgE to the most important food allergens, as well as to mixtures of household allergens in some cases (UniCAP System, Phadia AB). Results: Skin lesion in patients with EB masks allergic skin manifestations, causing a hypodiagnosis of the FA in this category of patients, which in turn leads to erroneous organization of nutritional support. FA (clinical manifestations) was identified in 20.7% of children with EB (in 10% of cases with simple form of EB and in 24.2% — in patients with dystrophic form of EB). Products containing cow’s milk protein, cereals, and eggs were identified as etiologic factors of FA in most cases. In the group of children with comorbidity FA and EB high and very high levels of total IgE (1000 kUA / l) were detected most frequently. The main cause-significant allergens are cow’s milk proteins, cereals, eggs. Conclusions: Comorbidity with FA is high in patients with dystrophic form of EB. The main cause-significant allergens are cow’s milk proteins, cereals, eggs.

Crossreactive allergen-specific IgE in children with birch pollen allergic rhinitis

Objective. The aim of this study was to research a sIgE allergen profile of birch pollen and to evaluate a contribution of some homologous food allergens as well as latex allergen to the development of sensibility in allergic rhinitis (AR) / rhinoconjunctivitis patients, in focus of cross-reactivity and oral allergy syndrome.. Methods. Blood sera of 21 AR/rhinoconjunctivitis patients (at the age of 3 to 16) and 20 healthy persons without allergy symptoms were used. sIgE to birch pollen, soybean, latex, apple and celery as well as the total IgE levels were measured by the ImmunoCAP method (Phadia, Sweden) and the ELISA kits (Alkorbio, Russia). Results. We detected high total IgE levels, sIgE to allergens of birch pollen, apple, celery, as well as to recombinant allergens of birch Bet v 1, Bet v 2 and soybean - Gly m 4 in AR patients. Correlation analysis of IgE humoral response to homologous proteins showed the direct valid dependence between the sIgE levels to birch isoallergen Bet v 1 and soy isoallergen Gly m 4 (r=0,84; p

Evaluation of allergic sensitization in Lebanese patients with allergic conjunctivitis.

To describe the profile of patients with allergic conjunctivitis (AC) regarding their demographics, symptomatology and specific allergen sensitization, in a Lebanese tertiary hospital. Cross-sectional study conducted at the Hôtel-Dieu de France hospital (Beirut, Lebanon) during a period of 18months. Patients with seasonal or perennial AC presenting for ophthalmic consultation had measurements of total and specific IgE. A matching group of patients with AC seen at the allergist office during the same period underwent skin prick tests (SPTs). Forty-four patients were enrolled for blood work by their ophthalmologists. Seasonal and perennial forms were almost equivalent. In total, 56.8% had positive specific IgE, with higher prevalence in patients with seasonal AC (p=0.002), other associated allergies particularly allergic rhinitis (p=0.002) or a family history of allergy (p=0.005). Ocular surface severity scales were not shown as predictors. High levels of total IgE were commonly detected in those with positive specific IgE. Thirty-eight patients were assessed with SPT, and all had a positive result for at least one allergen. Dust mites were found to be the most frequent allergens based upon both specific IgE (72%) and SPT (92%), followed by Parietaria and other pollens. In our study, dust mites mono- or co-sensitization is present in the majority of patients with AC, with odds of positivity being higher using SPT than specific IgE. The latter are found more readily in seasonal AC and in the presence of personal and family history of allergy.

Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy. Medical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components. Patients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, that is, the kallikreins (KLK)-5 and KLK-7, were observed as compared with controls, while reduced expression of lympho-epithelial Kazal-type-related inhibitor (LEKTI), filaggrin, E-cadherin, claudin, occludin, desmoglein-1 was found, independent of CS therapy. In CS-treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS-naive EoE. This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.

Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disorder of abnormal mast cells in at least 1 extracutaneous organ/tissue. Anaphylaxis is an acute, severe systemic hypersensitivity reaction, and a strong association between SM and anaphylaxis has been shown. However, not all patients with SM experience anaphylaxis. Presently, there are no predictive markers to discriminate patients with SM at high risk of anaphylaxis from those at low risk. This study sought to determine risk factors for the occurrence of anaphylaxis in patients with SM. A cross-sectional study was conducted in 122 consecutive adult patients with SM admitted to the Mastocytosis Center at Karolinska University Hospital. All patients underwent medical evaluation, including bone marrow biopsy and a thorough allergy workup. To determine risk factors, study subjects were categorized into 2 groups according to the presence (n= 55) or absence (n= 67) of anaphylaxis and compared for their demographic, clinical, and biochemical characteristics. Patients with SM with anaphylaxis had less frequent presence of mastocytosis in the skin (P < .001), more atopic predisposition (P= .021), higher total IgE levels (P < .001), and lower baseline tryptase levels (27 ng/mL vs 42 ng/mL; P= .024) compared with patients with SM without anaphylaxis. Patients with SM with anaphylaxis display unique clinical and laboratory features. Hence, a risk analysis tool that is capable of discriminating patients with SM at high risk of anaphylaxis from those at low risk with 86% sensitivity was developed by using the variables male sex, absence of mastocytosis in the skin, presence of atopy, IgE levels of 15 kU/L or more, and baseline tryptase levels of less than 40 ng/mL.

Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 1

Helminth infections and allergic diseases are associated with IgE hyperresponsiveness but the genetics of this phenotype remain to be defined. Susceptibility to Ascaris lumbricoides infection and antibody levels to this helminth are associated with polymorphisms in locus 13q33-34. We aimed to explore this and other genomic regions to identify genetic variants associated with the IgE responsiveness in humans. Forty-eight subjects from Cartagena, Colombia, with extreme values of specific IgE to Ascaris and ABA-1, a resistance marker of this nematode, were selected for targeted resequencing. Burden analyses were done comparing extreme groups for IgE values. One-hundred one SNPs were genotyped in 1258 individuals of two well-characterized populations from Colombia and Sweden. Two low-frequency coding variants in the gene encoding the Acidic Mammalian Chitinase (CHIA rs79500525, rs139812869, tagged by rs10494133) were found enriched in high IgE responders to ABA-1 and confirmed by genetic association analyses. The SNP rs4950928 in the Chitinase 3 Like 1 gene (CHI3L1) was associated with high IgE to ABA-1 in Colombians and with high IgE to Bet v 1 in the Swedish population. CHIA rs10494133 and ABDH13 rs3783118 were associated with IgE responses to Ascaris. SNPs in the Tumor Necrosis Factor Superfamily Member 13b gene (TNFSF13B) encoding the cytokine B cell activating Factor were associated with high levels of total IgE in both populations. This is the first report on the association between low-frequency and common variants in the chitinases-related genes CHIA and CHI3L1 with the intensity of specific IgE to ABA-1 in a population naturally exposed to Ascaris and with Bet v 1 in a Swedish population. Our results add new information about the genetic influences of human IgE responsiveness; since the genes encode for enzymes involved in the immune response to parasitic infections, they could be helpful for understanding helminth immunity and allergic responses. We also confirmed that TNFSF13B has an important and conserved role in the regulation of total IgE levels, which supports potential evolutionary links between helminth immunity and allergic response.

Association of Macrophage Migration Inhibitory Factor Polymorphisms with Total Plasma IgE Levels in Patients with Atopic Dermatitis in Korea.

The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, −173 G to C and −794 CATT5–8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The −173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF −794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the −173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the −794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE.