Low Immunoglobulin E Levels Research Articles

Relationship between autoimmune diseases and serum basal immunoglobulin E levels in patients with common variable immunodeficiency.

Background: Autoimmune diseases can occur at any time in patients with common variable immunodeficiency (CVID). However, the relationship between low immunoglobulin E (IgE) levels and autoimmune diseases in patients with CVID remains poorly understood. Objective: We aimed to determine the relationship between autoimmunity and low IgE in patients with CVID. Methods: This retrospective cohort study was conducted by using data that had been collected from 62 adult patients with CVID between April 2012 and December 2021. Serum basal IgE levels were compared between patients with and patients without autoimmune disease. Results: Overall, 23 of the 62 patients with CVID (37.1%) had at least one autoimmune disease (CVID-O). Autoimmune cytopenias, mainly immune thrombocytopenic purpura, were observed in half of all the patients. Other autoimmune diseases present among the patients included rheumatological diseases, inflammatory bowel diseases, lymphoma, granulomatous lymphocytic interstitial lung disease, autoimmune hepatitis, alopecia, and multiple sclerosis. Serum IgE levels were measured at the time of diagnosis; IgE was undetectable (<2.5 IU/mL) in 82.6% of the patients with CVID-O (n = 19). The median (interquartile range) serum IgE value in the patients with CVID-O was 2 IU/mL (1-16 IU/mL), which was significantly lower than the median serum IgE value in patients with CVID and without autoimmune disease (p < 0.001). Low IgE levels in patients with CVID-O were an independent risk factor for the development of autoimmune disease in patients with CVID (odds ratio 3.081 [95% confidence interval, 1.222-7.771]; p = 0.017). Conclusion: Low serum IgE levels were associated with the development of autoimmune disease in patients with CVID. The monitoring of serum IgE levels in patients with CVID may be useful in the early diagnosis and treatment of autoimmune diseases.

Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department

Background: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. Methods: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. Results: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. Conclusion: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.

Association of Maternal Asthma and Total Serum Immunoglobulin E levels with Obstetric Complications: The Japan Environment and Children's Study.

To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40IU/mL), moderate IgE levels (52.40-331.00IU/mL), and high IgE levels (> 331.00IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05-1.50) and 1.33 (95% CI, 1.06-1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73-0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04-1.52). MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA.

Relationship between low serum immunoglobulin E levels and malignancies in 9/11 World Trade Center responders

BackgroundIndividuals with very low immunoglobulin E (IgE) levels have a high risk of developing malignancy. Previous studies have revealed that World Trade Center (WTC) responders exposed to carcinogens have an elevated risk of some cancers. ObjectiveTo evaluate the association between low-serum IgE levels and cancer development in WTC-exposed responders. MethodsIgE levels were measured in 1851 WTC responders after September 11, 2001. This is the first pilot study in humans comparing the odds of developing cancer in this high-risk population, between the “low-IgE” (IgE in the lowest third percentile) vs “non–low-IgE” participants. ResultsA significantly higher proportion of hematologic malignancies was found in low-IgE (4/55, 7.3%) compared with non–low-IgE (26/1796, 1.5%, P < .01) responders. The proportion of solid tumors were similar in both groups (5.5% vs 11.4%, P > .05). After adjustment for relevant confounders (race, sex, age at blood draw, WTC arrival time, smoking status), the low-IgE participants had 7.81 times greater odds (95% confidence interval, 1.77-29.35) of developing hematologic cancer when compared with non–low-IgE participants. The hematologic cancers found in this cohort were leukemia (n = 1), multiple myeloma (n = 1), and lymphoma (n = 2). No statistical significance was found when estimating the odds ratio for solid tumors in relation to IgE levels. ConclusionWTC responders with low serum IgE levels had the highest odds of developing hematologic malignancies. This hypothesis-generating study suggests that low serum IgE levels might be associated with the development of specific malignancies in at-risk individuals exposed to carcinogens. Larger, multicenter studies with adequate follow-up of individuals with different IgE levels are needed to better evaluate this relationship.

Association of the CFTR gene with asthma and airway mucus hypersecretion.

Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results. (1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion. Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis. Genetic differences were observed in the c.1680-870T>A polymorphism of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011). The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM_000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.

Total IgE as a Marker for Chronic Spontaneous Urticaria.

ObjectiveImmunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed.MethodsPublications were searched via PubMed. The search terms used were “chronic urticaria” and “total IgE.” Studies were screened by titles and abstracts, and 141 were used in the review.ResultsCSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies.ConclusionThe results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.

Galactose-alpha-1,3-galactose syndrome.

The galactose-alpha-1,3-galactose (alpha-Gal) syndrome is a newly recognized and unique form of food allergy, characterized by delayed reactions to mammalian meats. This form of allergy occurs in individuals who become sensitized to alpha-Gal, a carbohydrate that is present on most mammalian tissues. Sensitization occurs after exposure to multiple arthropod bites, most commonly the lone star tick. Cases of the alpha-Gal syndrome are primarily found in the southeastern United States, which overlaps with the known geographic distribution of the lone star tick. Patients present with a history of delayed symptom onset, ~2-6 hours after ingestion of mammalian meat. As with other immunoglobulin E (IgE) mediated food allergic reactions, alpha-Gal reaction symptoms may include skin, respiratory, gastrointestinal, or cardiovascular systems, and severity may range from mild reactions to severe anaphylaxis. The diagnosis is based on the detection of alpha-Gal specific IgE (sIgE) as well as the total IgE value because some cases include patients with low total IgE levels but a high percentage of alpha-Gal sIgE to total serum IgE levels. Percutaneous testing with commercial meat skin-prick testing extracts is not a reliable tool for diagnosis. Prick-prick skin testing to fresh cooked meat may be considered, whereas intradermal testing to fresh meat is primarily reserved for research purposes. The mainstay of treatment involves avoidance of mammalian meat and medications that express the same carbohydrate antigen. With a small portion of patients, other meat-containing products should also be avoided if symptoms persist with mammalian meat avoidance alone. Prolonged avoidance of mammalian meat as well as avoidance of further tick bites can decrease alpha-Gal sIgE over time, and some patients are able to reintroduce mammalian meat into their diet.

Relevance of Low Specific IgE Levels to Egg, Milk and Peanut in Infancy

To evaluate the clinical importance of low specific immunoglobulin E (IgE) to hen’s egg, cow’s milk, and peanut at 6 months in relation to doctor’s diagnosis of allergy-related disease at 5 years of age.Families in Sweden were recruited between 2004 and 2011 (ALADDIN prospective birth cohort). This study included 372 children, all of whom contributed a blood sample at 6 months and at 1, 2, and/or 5 years of age. Fifty percent were girls, 17% were born via cesarean delivery, and 26% were breastfed exclusively for 6 months. At 6 months, 11% had a doctor’s diagnosis of asthma, 12% had a diagnosis of eczema, 3% had a diagnosis of allergic rhinoconjunctivitis, and 8% had a diagnosis of food allergy.Questionnaires regarding lifestyle, background, diet, and health were completed at enrollment, 2 and 6 months, and 1, 2, and 5 years of age. Serum IgE to specific foods and aeroallergens was measured in children at 6 months and 1, 2, and 5 years. For the statistical analysis, 3 categories were designated: nonsensitized (<0.1 kU/L), low sensitized (0.1–0.34 kU/L), and sensitized (≥0.35 kU/L); proportion with allergy-related disease was assessed.For egg and milk, having specific IgE in the interval of 0.1 to 0.34 kU/L at 6 months was significantly associated with being sensitized (≥0.35 kU/L) to that specific allergen at 1 year (P = .01 and <.01, respectively) and to aeroallergens at 5 years (P = <.01 and .01), compared with nonsensitized children. Being sensitized (≥0.35 kU/L) to egg or milk at 6 months was significantly associated with sensitization to the food at 1 and 2 years of age and to any food allergen, but it was not associated with aeroallergen sensitization at 5 years as compared with those with low sensitization (P = .69). Approximately 50% of children with low sensitization to milk or egg at 6 months had IgE that declined to nonsensitized levels at 2 years of age. For peanut, low sensitization at 6 months was only significantly associated with being sensitized to aeroallergens at 5 years of age (P = .04). Low-level sensitization to egg was associated with higher rates of eczema (P < .01).Specific IgE to milk, egg, and peanut in the range of 0.1 to 0.34 kU/L at 6 months appeared to decrease over time. However, low-level sensitization at 6 months appeared to increase the likelihood of sensitization to aeroallergens at 5 years. Compared with those who were nonsensitized at 6 months, children with low sensitization to milk or egg had higher rates of sensitization to that allergen at 1 year of age. Having low sensitization to egg at 6 months was associated with the development of eczema.Researchers in this study evaluated whether specific IgE at 6 months was associated with further IgE sensitization and allergy-related diagnosis. The strengths of the study include that it was population based and managed children over the course of 5 years. The study does not provide any data about the development of clinical food allergy. This study suggests that children with low sensitization at 6 months can be counseled that ∼50% had undetectable IgE to the relevant allergen at 2 years, but the low sensitization could suggest a higher risk of future aeroallergen sensitization as well as potentially eczema for those with egg-specific IgE.

Milk-Related Symptoms and Immunoglobulin E Reactivity in Swedish Children from Early Life to Adolescence.

Cow’s milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kUA/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kUA/L, 8y: 0.72 kUA/L; 16 years: 1.1 kUA/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. Of the 301 assessable patients (mean age: 60.9±9.3years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P=0.006). Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

Normal serum IgE levels and eosinophil counts exhibited during Strongyloides stercoralis infection

Infections with parasites, such as Strongyloides stercoralis, typically cause elevated levels of serum immunoglobulin E (IgE) and eosinophils; however, co-infection with human T cell lymphotropic virus type 1 (HTLV-1) can cause lower levels of serum IgE during S. stercoralis infection. We conducted this study to determine whether serum IgE levels and eosinophil counts could also be related to other patient characteristics or symptoms. Between 1991 and 2014, we measured and compared the symptoms of 237 patients and evaluated serum IgE levels and eosinophil counts of 199 patients who were infected with S. stercoralis at the Ryukyu University Hospital and the Nishizaki Hospital. Medical records were reviewed and blood samples were taken before treatment with the anthelminthic, ivermectin, 2weeks following the first dosage, and 2weeks following the second dosage. Commonly reported symptoms included abdominal pain, diarrhea, and general fatigue. Serum IgE levels were found to be normal in patients co-infected with HTLV-1. Additionally, females and patients younger than 70years old exhibited normal serum IgE levels when infected with S. stercoralis. No factor included in our analysis was found to affect eosinophil counts. Serum IgE levels can remain within the normal range for some patients infected with S. stercoralis. Therefore, physicians should not eliminate S. stercoralis infection from the differential diagnosis solely according to findings of normal or low IgE levels.

Erythrodermic cutaneous T-cell lymphoma: How to differentiate this rare disease from atopic dermatitis

Sézary syndrome and erythrodermic mycosis fungoides have been recognized as part of a broader spectrum of erythrodermic cutaneous T-cell lymphoma (E-CTCL). Atopic dermatitis (AD) is the most common, chronic inflammatory skin disease and can, in its most severe form, manifest as erythroderma. It is often difficult to clinically distinguish E-CTCL from various common and benign diseases presenting as erythroderma, including AD. Differentiating E-CTCL from benign inflammatory diseases is important to ensure proper disease management, and to provide accurate prognostic information. Clinical and laboratory features, including pruritus and serum levels of soluble interleukin-2 receptor, lactate dehydrogenase (LDH), immunoglobulin E (IgE), and several chemokines, do not differentiate E-CTCL from AD. In contrast, low serum allergen-specific IgE levels, presence of Sézary cells in peripheral blood, histological findings, and high CD4/CD8 ratio and CCR10 positivity in lesional skin are helpful in reaching a correct diagnosis. Patients with E-CTCL have been treated with oral etretinate, intravenous or subcutaneous interferon, bexarotene, extracorporeal photopheresis, total body surface electron beam, chemotherapy, or any combination of these modalities. Older patients, high serum LDH levels, and high number of circulating atypical lymphocytes are associated with poor prognosis.

High plasma IgE levels within the Scandinavian wolf population, and its implications for mammalian IgE homeostasis

Immunoglobulin E (IgE) serves as an important link between innate and adaptive immunity through its ability to bind high affinity receptors on mast cells and basophils. Large differences in IgE levels may here affect this important link, and IgE levels in natural non-domestic animal populations may therefore be very informative concerning the levels of IgE that this system have been balanced against during recent mammalian evolution. However, very few such studies have been performed. Here, we present an analysis of total IgE levels in 65 Scandinavian wolves: 57 free living (wild), and 8 wolves in captivity (Zoo). The 57 wild wolves correspond to approximately 30% of the entire wolf population in Sweden and Norway and thus represent a large fraction of the entire population, making this a unique sample from a wild canine population. The median IgE level in these wolves was 67 μg/ml, which is approximately twice the level seen in domestic dogs and more than 100 times the levels in non-atopic humans. The collected information from domestic and wild populations now indicate that the very low IgE levels observed in man and laboratory rodents are most likely an effect of a life in a relatively parasite free environment, and that total IgE levels under maximally stimulatory (normal) conditions may reach 100–200 μg/ml.

Eosinophilic esophagitis in adults – no clinical relevance of wheat and rye sensitizations

Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.

IgE antibody in the serum--detection and diagnostic significance.

IgE antibody in the serum--detection and diagnostic significance.

Immunoglobulin E production in chronic pancreatitis

Objectives Serum immunoglobulin E (IgE) was investigated in patients with chronic pancreatitis in order to elucidate possible disease mechanisms linking pancreatitis, adverse reaction to foods and allergy. Design and methods Serum IgE was analysed in 86 nonatopic patients with advanced chronic pancreatitis and 54 non-atopic controls. IgE detection was performed by enzyme-linked immunofluorescence. Results Mean IgE levels (± standard error of mean) in chronic pancreatitis patients (286.1 ± 49 kU/l) were found to be significantly elevated compared to controls (67.7 ± 11 kU/l; P < 0.0001). Normal IgE levels (< 100 kU/l) were present in 40/54 control patients (74.1%), but only 39/86 pancreatitis patients (45.3%). Of the patients with chronic pancreatitis, 47/86 (54.6%) had clearly elevated IgE levels of > 100 kU/l and their IgE values did not show a Gaussian distribution. However, nine-fold higher IgE levels were found in chronic pancreatitis patients with alcohol consumption of > 25 g/day and exocrine insufficiency (915.5 ± 240 kU/l) than in pancreatitis patients with normal exocrine function and no alcohol consumption (103.4 ± 43 kU/l; P < 0.001). Moreover, acute episodes of chronic pancreatitis were found to increase serum IgE levels. Conclusions In patients with chronic pancreatitis, serum IgE production is markedly enhanced, especially during acute inflammatory episodes or when alcohol is consumed. Since abstinence from alcohol and pancreatic enzyme substitution are associated with clearly lower IgE levels, it may be concluded that pancreatic insufficiency with reduced nutrient digestion and alcohol consumption stimulate IgE production. This finding gives rise to the speculation that, apart from pancreatic inflammation, cross-linking of IgE with alimentary or other antigens might be involved in the pathophysiology of a subpopulation of patients with chronic pancreatitis and manifest pancreatic insufficiency.

Immunoglobulin E production in chronic pancreatitis.

Serum immunoglobulin E (IgE) was investigated in patients with chronic pancreatitis in order to elucidate possible disease mechanisms linking pancreatitis, adverse reaction to foods and allergy. Serum IgE was analysed in 86 non-atopic patients with advanced chronic pancreatitis and 54 non-atopic controls. IgE detection was performed by enzyme-linked immunofluorescence. Mean IgE levels (+/- standard error of mean) in chronic pancreatitis patients (286.1+/-49 kU/l) were found to be significantly elevated compared to controls (67.7+/-11 kU/l; P<0.0001). Normal IgE levels (<100 kU/l) were present in 40/54 control patients (74.1%), but only 39/86 pancreatitis patients (45.3%). Of the patients with chronic pancreatitis, 47/86 (54.6%) had clearly elevated IgE levels of >100 kU/l and their IgE values did not show a Gaussian distribution. However, nine-fold higher IgE levels were found in chronic pancreatitis patients with alcohol consumption of >25 g/day and exocrine insufficiency (915.5+/-240 kU/l) than in pancreatitis patients with normal exocrine function and no alcohol consumption (103.4+/-43 kU/l; P<0.001). Moreover, acute episodes of chronic pancreatitis were found to increase serum IgE levels. In patients with chronic pancreatitis, serum IgE production is markedly enhanced, especially during acute inflammatory episodes or when alcohol is consumed. Since abstinence from alcohol and pancreatic enzyme substitution are associated with clearly lower IgE levels, it may be concluded that pancreatic insufficiency with reduced nutrient digestion and alcohol consumption stimulate IgE production. This finding gives rise to the speculation that, apart from pancreatic inflammation, cross-linking of IgE with alimentary or other antigens might be involved in the pathophysiology of a sub-population of patients with chronic pancreatitis and manifest pancreatic insufficiency.

The Natural History of Peanut Allergy in Young Children and Its Association with Serum Peanut-Specific IgE

Purpose of the Study. To characterize adverse reactions after accidental peanut exposure in young children with peanut allergy and to determine the usefulness of serum peanut-specific immunoglobulin E (IgE) levels during follow-up.Study Population. One hundred two children were identified who had clinical peanut hypersensitivity before 4 years of age. Inclusion criteria included 1) a convincing history of clinical peanut hypersensitivity and/or a positive double-blind, placebo-controlled food challenge (DBPCFC) response to peanuts and 2) a positive skin prick test response to peanuts.Methods. Research subjects were contacted at least yearly to track adverse reactions caused by accidental exposure to peanuts. Nineteen participants discontinued their participation in the study or were lost to follow-up, leaving 83 for inclusion in the analysis. Peanut-specific serum IgE levels were determined in 51 of 83 subjects using the Pharmacia CAP system (Uppsala, Sweden).Results. Thirty-one of 53 (58%) of the subjects followed for 5 years experienced adverse reactions from accidental peanut exposure. Regardless of the nature of their initial reaction, the majority with subsequent reactions (31/60; 52%) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51; 22%) had lower serum peanut-specific IgE levels (median: 1.25 kUa/L vs 11.65 kUa/L; P = .004; Wilcoxan rank sum) than the group with respiratory and/or gastrointestinal symptoms (40/51; 78%). There was no threshold level below which only skin symptoms appeared to occur. Of note, 4 subjects had negative DBPCFC results to peanuts during the follow-up period.Conclusions. The majority of children with peanut allergy followed for up to 5 years will have adverse reactions from accidental peanut exposure. Symptoms may not be consistent with symptoms reported during initial reactions. A minority of children with peanut allergy can lose their clinical hypersensitivity.Reviewer’s Comments. This report addresses 2 common questions asked by parents of children with peanut allergy: a) will the reactions become progressively worse? and b) will the reactions ever subside? Despite appropriate counseling on peanut avoidance, the majority of the children experienced an accidental peanut ingestion during follow-up. Moreover, initial clinical reactions involving only the skin can subsequently progress to involve the respiratory and/or gastrointestinal systems. A minority of subjects with low serum peanut-specific IgE levels developed oral tolerance to peanut. This investigation has expanded the growing body of evidence in this research area and has provided practical clinical information for addressing allergic reactions to peanuts. With the inevitability of accidental ingestions, the general trend for worsening of clinical reactions with subsequent exposures, and the inability to predict severity of future reactions, the take-home messages should be that all patients with peanut allergy need proper education about the potential seriousness of future accidental exposures and self-injectable epinephrine to manage future, severe allergic reactions.

The use of chimeric human Fc(epsilon) receptor I to redirect cytotoxic T lymphocytes to tumors.

Chimeric receptors that redirect effector cell function to tumor cells or virus-infected cells have received much attention. Given the high affinity of Fc(epsilon)RI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fc(epsilon) receptor may provide a novel, versatile, and effective anti-tumor strategy. We have used a mouse perforin 5'-promoter to express a single-chain human Fc(epsilon) receptor in the mouse cytotoxic T lymphocyte cell line, CTLL-R8. Upon ligation of the chimeric Fc(epsilon) receptors by IgE, a signal for effector function is transmitted via the intracellular domain of CD3zeta. Selection in G418-containing medium produced CTLLR8 transfectant clones that: (1) expressed chimeric Fc(epsilon) receptor as determined by flow cytometry; (2) bound human IgE antibodies with high affinity as determined by Scatchard analysis; (3) specifically rosetted IgE-coated SRBC; (4) lysed target cells in IgE-mediated ADCC and reverse ADCC assays; and (5) retarded tumor growth in a Winn assay. Therefore these chimeric Fc(epsilon) receptors can effectively redirect cytotoxicity to tumor cells. Future efforts will assess the versatility and efficacy of these IgE-binding chimeric receptors to redirect killer cell function in animal tumor models.

CIRCULATING LEVELS OF IMMUNOGLOBULIN E IN PATIENTS WITH CANCER

Circulating levels of immunoglobulin E (IgE) have been determined by solidphase radioimmunoassay and by radial immuno-diffusion technique in healthy controls and in a large group of patients with advanced cancer. The mean level in the control group, as determined by radioimmunoassay, was 215 units per ml. (range 85-740). In patients receiving cytotoxic drugs, the mean level was significantly lower, and most had values below the normal range. Similar findings were obtained in approximately half the patients with advanced, untreated neoplasms, and there was a close correlation between the results obtained by the two assays in the controls and in these cancer patients. Conversely, the remaining patients with untreated neoplasms had low or undetectable IgE levels as determined by radial immunodiffusion, but apparently very high values (usually more than 100,000 units per ml.) by radioimmunoassay. Additional studies indicated that the high immunoreactive levels were an artefact due to the presence of a circulating inhibitor.