A Novel Method for Total IgE Purification from Human Serum.

For Ab purification, high-affinity chromatography is commonly used. This technique results in high-purity Abs, but it requires highly specific knowledge and equipment. Commercial kits for purification of IgE are not available. Therefore, we established a (to our knowledge) novel method for the purification of total IgE from human serum. Sera from 19 allergic and nonallergic patients were included. After depletion of polyclonal IgG, total serum IgE was captured using anti-human IgE Abs coupled to beads, eluted from the beads, and incubated with protein G-coupled beads to increase the final purity. Purity analysis and Ab detection were performed by Western blot. Total serum IgE and purified IgE concentrations were analyzed using ELISA. To determine their functionality, primary human mast cells were sensitized with purified IgE and activated with anti-IgE or a relevant allergen. CD63+ expression and histamine release were used as readout parameters. Concentrations of purified total IgE corresponded with the levels of total serum IgE. Minor fractions of IgE remained attached to the beads, confirming an effective elution of IgE Abs. Only minimal amounts of IgG were found in the purified IgE fractions, confirming a high purity of IgE. Mast cells sensitized with purified IgE and subsequent activation with anti-IgE Ab or a relevant allergen showed increased expression of CD63+ and increased histamine release. This (to our knowledge) novel method represents a highly effective and widely accessible approach for purification of human serum IgE, which can improve the use of IgE-based in vivo and in vitro models and contribute to allergy research.

Treatment of acute urticaria: A systematic review.

There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence-based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk-of-bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H1 and/ or H2 -antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state-of-the-art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well-designed, high-quality interventional trials are needed to establish evidence-based treatment guidelines for AU.

Immunoglobulin E autoantibodies in atopic dermatitis associate with Type-2 comorbidities and the atopic march.

BACKGROUND: Autoreactive immunoglobulin E (IgE) antibodies to self-peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well-characterized patients with AD and controls (1.2-88.9 years). METHODS: Atopic dermatitis patients were sub-grouped in AD with comorbid Type-2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type-2 diseases ("atopic controls," n = 52) and non-atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. RESULTS: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD-patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean-section and diversity of domestic pets. CONCLUSIONS: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.

History of Allergy: Clinical Descriptions, Pathophysiology, and Treatment.

Allergy has shown a dramatic increase in prevalence in the last decades. However, allergic diseases are probably not new. Asthma and eczema have been described in ancient societies like Egypt, China and in the Greco-Roman culture. In the middle-ages descriptions of hay fever can be found in Persian-Arabian literature (called "rose fever"). Scientific allergology started in the nineteenth century with descriptions of hay fever and experimental studies showing pollen as elicitors. Milestones in the twentieth century comprise the description of anaphylaxis, the creation of the terms "allergy" and "atopy", the Prausnitz-Küstner test and finally the discovery of IgE and the development of the Radio-Allergo-Sorbent-Test (RAST) for routine detection of specific IgE antibodies. Progress in cellular immunology led to the description of T-cell subsets Th1 and Th2. Mast cell and basophil research progressed since the first description to histamine release studies. Leukotrienes were detected. Pharmacotherapy started in the early twentieth century with adrenaline (epinephrine) followed by antihistamines and cortisone. Allergen-specific immunotherapy was introduced. Epidemiologic studies pointed to a role of environmental pollutants as allergy enhancing factors and protective influences from farm environment. Through the progress in experimental allergology and immunology targeted therapeutics have been developed for various atopic conditions.

Autoreactive T cells and their role in atopic dermatitis.

Atopic dermatitis (AD) is an itchy, non-contagious relapsing and chronic inflammatory skin disease that usually develops in early childhood. This pathology is associated with food allergy, allergic asthma, allergic rhinitis and anaphylaxis which may persist in adulthood. The underlying mechanisms of AD (endotypes) are just beginning to be discovered and show a complex interaction of various pathways including skin barrier function and immune deviation. Immune reactions to self-proteins (autoantigens) of the skin have been identified in patients with inflammatory skin diseases, such as chronic spontaneous urticaria, connective tissue disease, pemphigus vulgaris and bullous pemphigoid. IgE antibodies and T cells directed against epitopes of the skin were observed in adult patients with severe and chronic AD as well. This was associated with disease severity and suggests a progression from allergic inflammation to severe autoimmune processes against the skin. IgE-mediated autoimmunity and self-reactive T cells might accelerate the ongoing skin inflammation or might contribute to the relapsing course of the disease. However, to date, the exact mechanisms of IgE-mediated autoimmunity and self-reactive T cells in the pathophysiology of AD are still unclear. The aim of this review is to evaluate the development of (autoreactive) T cells and their response to (auto)antigens, as well as the role of the peripheral tolerance in autoimmunity in the pathophysiology of AD, including the unmet needs and gaps.

Physiology and pathology of eosinophils: Recent developments: Summary of the Focus Workshop Organized by DGAKI.

Over the last century, eosinophils have been regarded ambiguously either as 'friends' or 'foes'. Recent developments have greatly enhanced our understanding of the role and function of eosinophils in health and disease. Pathogenic eosinophilic inflammation can lead to severe diseases in various organs, such as the gastrointestinal tract, airways, heart and skin. In a 2-day focus workshop of the German Society for Allergology and Clinical Immunology (DGAKI), the state of the art was discussed and practical recommendations for diagnosis and treatment of eosinophilic diseases, with a particular focus on new biologics, such as anti-interleukin 5 and anti-interleukin 5R, were derived.

ARIA-EAACI statement on severe allergic reactions to COVID-19 vaccines - An EAACI-ARIA Position Paper.

Further to the approval of the Coronavirus disease 2019 (COVID-19) vaccine BNT162b2, several severe anaphylaxis cases occured within the first few days of public vaccination. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and there are raising concerns that severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerge. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal, all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as this could have a significant impact on reaching the goal of population immunity. Healthcare practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly with the ability to administer adrenaline. Further to vaccine administration, a mandatory observation period of at least 15 minutes should be followed for all individuals. The current data have not shown any higher risk for patients suffering from allergic rhinitis or asthma, and this message should be clearly stated by physicians to enable our patients to trust the vaccine. More than 30% of the population suffers from allergic diseases and the benefit of the vaccination clearly outweighs the risk of severe COVID-19 development.

History of the Collegium Internationale Allergologicum: A Very Special Society Devoted to Allergy and Immunology.

The Collegium Internationale Allergologicum (CIA) was founded on 15 October 1954 in London by a group of 48 international allergists and immunologists from 18 countries of all continents, among them such distinguished scientists as Carl Prausnitz-Giles, Sir Henry Dale, Paul Kallos, and many others. Contrary to other international associations in the field, this Collegium limited the number of members in order to allow more intense and open discussions in "the humble spirit of scientific enquiry, friendly cooperation, good fellowship and professional relationships in the field of allergy" as stated in the statutes. It is not possible to apply for membership, and one has to be proposed by at least 2 CIA members and invited to present at least once at a symposium. Over the decades, a rhythm of biannual symposia developed, the 32nd held in Palma de Mallorca in October 2018. These symposia went around the world from London, Rome, Copenhagen, New Orleans, Puerto Vallarta, Nantucket, Hakone, Konstanz, Goeteborg, and Sorrento, just to name a few places. Preferably they were held on islands such as Capri, Corfu, Martinique, Curacao, Bornholm, Malta, and Ischia in order to make it more difficult for people to arrive late or leave early. It is expected that participants stay over the whole length of the 5-day symposium. On these symposia, it is good custom to also present unpublished data, so participants get the latest news. The most important developments in the field of Allergy and Clinical Immunology have been discussed at early stage and sometimes by speakers who later won the Nobel Prize. While all presentations are equal, be it oral communications or posters, there are 3 special lectures, namely the Carl Prausnitz lecture, the Paul Kallos lecture, and a "Relaxing from Immunology" lecture which can be devoted to any interesting topic not necessarily related to medicine or allergy. Since many years, the contents of the symposium are published in a proceedings volume, over a longtime printed within the "International Archives of Allergy and Immunology" which until now is the official journal of the Collegium. Participants agree that in the flood of more and more scientific congresses and larger events, the CIA Symposia are unique in their openness and friendly scientific interchange.

Figurate erythemas - update and diagnostic approach.

Figurate erythemas (FE) represent an etiopathophysiologically heterogeneous group of diseases defined by their characteristic annular erythematous skin lesions. Diagnosis is made primarily by clinical examination together with histological findings; often it is a diagnosis made by exclusion. While some authors discuss FE as clinical reaction pattern rather than distinct clinical entities, others identify four classic FE: erythema annulare centrifugum, erythema gyratum repens, erythema migrans and erythema marginatum. The differential diagnoses of FE are numerous and often challenging. We therefore present a potential diagnostic algorithm for FE that discriminates the differentials according to their temporal evolution and the clinical/histological phenotype of the various subtypes. Since some FE may present with an underlying malignancy, diligent clinicians are needed when dealing with those entities.

Different Psychosocial Factors Are Associated with Seasonal and Perennial Allergies in Adults: Cross-Sectional Results of the KORA FF4 Study.

BACKGROUND: Psychosocial factors are supposed to play a central role in the development of allergic diseases. Associations with seasonal and perennial forms of allergies have not been investigated, yet. OBJECTIVES: The aim of the study was to investigate the associations of psychosocial factors (social status, depression, generalized anxiety, psychosocial stress, Type-D personality) with seasonal, perennial, and other forms of allergies in adults. METHOD: The analysis of self-reported data of the KORA FF4 study was performed with SAS 9.4. The sample consisted of 1,782 study participants in the study region of Augsburg (39-88 years, 61 years, 51.1% female). Descriptive bivariate statistics and multinomial logistic regression models were performed. Age, sex, family predisposition, and smoking status were considered possible confounders. Moreover, several sensitivity analyses were carried out to check whether missing values distorted the results. RESULTS: A positive association between generalized anxiety and seasonal allergies was found in the multivariate model. Depression was positively, and anxiety negatively, associated with perennial allergies. No association between the analyzed psychosocial factors and other forms of allergies could be found. CONCLUSION: The results support the relevance of psychosocial factors in association with allergies. Looking at the psychosocial factors, a separate consideration of seasonal and perennial allergies seems reasonable. Further longitudinal studies should investigate the direction of the associations, the underlying mechanisms, and other psychosocial factors, such as coping mechanisms, in confirmed allergies.

Out-of-pocket Costs for Individuals with Atopic Eczema: A Cross-sectional Study in Nine European Countries.

Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are limited. To estimate the annual extra out-of-pocket spending due to AE among patients in Europe, a cross-sectional study using computer-assisted phone interviewing of patients with AE was performed in 9 European countries. A total of 1,189 patients (56% women) with AE, who were either eligible for, or on, systemic treatment, participated in the study between October 2017 and March 2018. Mean extra spending on everyday necessities was €927 per patient per year for healthcare expenses, and this figure was slightly, but not statistically significantly, influenced by the severity of AE. Emollients and moisturizers accounted for the highest monthly costs, followed by medication that was not reimbursed, doctors' and hospital costs. AE-related out-of-pocket costs pose a substantial burden for affected individuals, are higher than in other chronic diseases, and should always be included in economic assessments of the impact of this disease.

Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32.

BACKGROUND: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. OBJECTIVE: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma. METHODS: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 µg, n = 60) or high dose (160 µg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. RESULTS: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. CONCLUSIONS: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.