TY - JOUR AB - Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related increase of the serum tryptase level beyond the individual's baseline and a response of the symptomatology to drugs directed against mast cells, mast cell-derived mediators, or mediator effects. A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of MCASs. These conditions include hereditary alpha tryptasemia, mastocytosis with an expansion of clonal KIT-mutated mast cells, atopic diathesis, and overt IgE-dependent and IgE-independent allergies. Several of these conditions have overlapping definitions and diagnostic criteria and may also develop concomitantly in the same patient. However, although criteria and clinical features overlap, each of these conditions is characterized by a unique constellation of variables and diagnostic criteria. Since two, three, or more conditions can coexist in the same patient, with obvious clinical implications, it is of crucial importance to diagnose the variant of MCAS precisely and to take all accompanying, underlying and potentially complicating conditions, and comorbidities into account when establishing the management plan. Indeed, most of these patients require multidisciplinary investigations and only a personalized treatment approach can lead to an optimal management plan providing an optimal quality of life and low risk of anaphylaxis. AU - Valent, P.* AU - Hartmann, K.* AU - Bonadonna, P.* AU - Niedoszytko, M.* AU - Triggiani, M.* AU - Arock, M.* AU - Brockow, K. C1 - 65066 C2 - 52656 SP - 693-705 TI - Mast cell activation syndromes: Collegium Internationale Allergologicum Update 2022. JO - Int. Arch. Allergy Immunol. VL - 183 IS - 7 PY - 2022 SN - 1018-2438 ER - TY - JOUR AB - This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU. AU - Maurer, M.* AU - Eyerich, K.* AU - Eyerich, S. AU - Ferrer, M.* AU - Gutermuth, J.* AU - Hartmann, K.* AU - Jakob, T.* AU - Kapp, A.* AU - Kolkhir, P.* AU - Larenas-Linnemann, D.* AU - Park, H.S.* AU - Pejler, G.* AU - Sánchez-Borges, M.* AU - Schäkel, K.* AU - Simon, D.* AU - Simon, H.U.* AU - Weller, K.* AU - Zuberbier, T.* AU - Metz, M.* C1 - 58866 C2 - 48583 CY - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland SP - 321-333 TI - Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020. JO - Int. Arch. Allergy Immunol. VL - 181 IS - 5 PB - Karger PY - 2020 SN - 1018-2438 ER - TY - JOUR AB - Background: Assessing high-sensitivity C-reactive protein (hs-CRP) in relation to allergic endpoints can shed light on both the mechanisms of allergic disease development and early non-communicable disease prevention. However, only a few epidemiological studies so far have investigated the relationship in children and adolescents, and the results were mixed. Objectives: We sought to examine the interrelation between hs-CRP levels and allergic outcomes using a larger population size and a longitudinal study design. Methods: Complete data were available on 1,955 participants from the 15-years follow-up of the 2 large populationbased German birth cohorts -GINIplus and LISA. Serum hsCRP concentrations were measured using the immunoturbidimetric high-sensitive assay. Six allergic endpoints were used -doctor-diagnosed asthma, doctor-diagnosed eczema, doctor-diagnosed allergic rhinitis, food sensitization, aeroallergen sensitization, and any sensitization. We used generalized estimation equation models to assess the asso-ciations between hs-CRP levels and allergic endpoints. Results: Our longitudinal analyses did not detect any significant association between hs-CRP levels and any of the studied allergic outcomes (e.g., asthma, eczema, allergic rhinitis, food sensitization, aeroallergen sensitization, and any sensitization). The results were consistent in a series of sensitivity analyses. Conclusions: Our study suggests that there is no association between hs-CRP levels and any of the allergic endpoints in German adolescents. However, whether allergic diseases are inflammatory conditions and which markers might be most sensitive, remain to be confirmed in future studies. AU - Yang, B.-Y. AU - Markevych, I. AU - Harris, C. AU - Standl, M. AU - Schikowski, T.* AU - Koletzko, S.* AU - Herberth, G.* AU - Bauer, C.P.* AU - von Berg, A.* AU - Berdel, D.* AU - Dong, G.H.* AU - Heinrich, J. C1 - 55801 C2 - 46597 CY - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland SP - 152-157 TI - High-sensitivity C-reactive protein and allergic endpoints in German adolescents. JO - Int. Arch. Allergy Immunol. VL - 179 IS - 2 PB - Karger PY - 2019 SN - 1018-2438 ER - TY - JOUR AB - 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. AU - Zeiser, K. AU - Hammel, G. AU - Krabiell, L. AU - Linkohr, B. AU - Peters, A. AU - Schwettmann, L. AU - Ring, J.* AU - Johar, H. AU - Ladwig, K.-H. AU - Traidl-Hoffmann, C. C1 - 55925 C2 - 46691 CY - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland SP - 262-272 TI - Different psychosocial factors are associated with seasonal and perennial allergies in adults: Cross-sectional results of the KORA FF4 study. JO - Int. Arch. Allergy Immunol. VL - 179 IS - 4 PB - Karger PY - 2019 SN - 1018-2438 ER - TY - JOUR AB - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states. AU - Chaker, A. AU - Zissler, U.M. AU - Poulos, N.* AU - Wagenmann, M.* AU - Bas, M.* AU - Gürth, F. AU - Xanthou, G.* AU - Schmidt-Weber, C.B. C1 - 53406 C2 - 44850 CY - 6-9 Carlton House Terrace, London Sw1y 5ag, England SP - 15-25 TI - Activin-A is a pro-inflammatory regulator in type-2-driven upper airway disease. JO - Int. Arch. Allergy Immunol. VL - 176 IS - 1 PB - Royal Soc PY - 2018 SN - 1018-2438 ER - TY - JOUR AB - BACKGROUND: Pollen are monitored in Europe by a network of about 400 pollen traps, all operated manually. To date, automated pollen monitoring has only been feasible in areas with limited variability in pollen species. There is a need for rapid reporting of airborne pollen as well as for alleviating the workload of manual operation. We report our experience with a fully automated, image recognition-based pollen monitoring system, BAA500. METHODS: The BAA500 sampled ambient air intermittently with a 3-stage virtual impactor at 60 m(3)/h in Munich, Germany. Pollen is deposited on a sticky surface that was regularly moved to a microscope equipped with a CCD camera. Images of the pollen were constructed and compared with a library of known samples. A Hirst-type pollen trap was operated simultaneously. RESULTS: Over 480,000 particles sampled with the BAA500 were both manually and automatically identified, of which about 46,000 were pollen. Of the automatically reported pollen, 93.3% were correctly recognized. However, compared with manual identification, 27.8% of the captured pollen were missing in the automatic report, with most reported as unknown pollen. Salix pollen grains were not identified satisfactorily. The daily pollen concentrations reported by a Hirst-type pollen trap and the BAA500 were highly correlated (r = 0.98). CONCLUSIONS: The BAA500 is a functional automated pollen counter. Its software can be upgraded, and so we expected its performance to improve upon training. Automated pollen counting has great potential for workload reduction and rapid online pollen reporting. AU - Oteros, J. AU - Pusch, G. AU - Weichenmeier, I. AU - Heimann, U.* AU - Moller, R.S.* AU - Röseler, S.* AU - Traidl-Hoffmann, C. AU - Schmidt-Weber, C.B. AU - Buters, J.T.M. C1 - 46630 C2 - 37650 CY - Basel SP - 158-166 TI - Automatic and online pollen monitoring. JO - Int. Arch. Allergy Immunol. VL - 167 IS - 3 PB - Karger PY - 2015 SN - 1018-2438 ER - TY - JOUR AB - Background: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts. Methods: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up. Results: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children. Conclusions: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe. AU - Hohmann, C.* AU - Pinart, M.* AU - Tischer, C.G. AU - Gehring, U.* AU - Heinrich, J. AU - Kull, I.* AU - Melén, E.* AU - Smit, H.A.* AU - Torrent, M.* AU - Wijga, A.H.* AU - Wickman, M.* AU - Bachert, C.* AU - Lødrup Carlsen, K.C.* AU - Carlsen, K.H.* AU - Bindslev-Jensen, C.* AU - Eller, E.* AU - Esplugues, A.* AU - Fantini, M.P.* AU - Annesi-Maesano, I.* AU - Momas, I.* AU - Porta, D.* AU - Vassilaki, M.* AU - Waiblinger, D.* AU - Sunyer, J.* AU - Antò, J.M.* AU - Bousquet, J.* AU - Keil, T.* C1 - 30911 C2 - 34008 CY - Basel SP - 215-224 TI - The development of the MeDALL core questionnaires for a harmonized follow-up assessment of eleven European birth cohorts on asthma and allergies. JO - Int. Arch. Allergy Immunol. VL - 163 IS - 3 PB - Karger PY - 2014 SN - 1018-2438 ER - TY - JOUR AB - Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe. AU - Accordini, S.* AU - Corsico, A.G.* AU - Braggion, M.* AU - Gerbase, M.W.* AU - Gislason, D.* AU - Gulsvik, A.* AU - Heinrich, J. AU - Janson, C.* AU - Jarvis, D.* AU - Jõgi, R.* AU - Pin, I.* AU - Schoefer, Y. AU - Bugiani, M.* AU - Cazzoletti, L.* AU - Cerveri, I.* AU - Marcon, A.* AU - de Marco, R.* C1 - 11480 C2 - 30753 SP - 93-101 TI - The cost of persistent asthma in Europe: An international population-based study in adults. JO - Int. Arch. Allergy Immunol. VL - 160 IS - 1 PB - Karger PY - 2013 SN - 1018-2438 ER - TY - JOUR AB - Long-term birth cohort studies are essential to understanding the life course and childhood predictors of allergy and the complex interplay between genes and the environment (including lifestyle and socioeconomic determinants). Over 100 cohorts focusing on asthma and allergy have been initiated in the world over the past 30 years. Since 2004, several research initiatives funded under the EU Framework Program for Research and Technological Development FP6-FP7 have attempted to identify, compare, and evaluate pooling data from existing European birth cohorts (GA(2)LEN: Global Allergy and European Network, FP6; ENRIECO: Environmental Health Risks in European Birth Cohorts, FP7; CHICOS: Developing a Child Cohort Research Strategy for Europe, FP7; MeDALL: Mechanisms of the Development of ALLergy, FP7). However, there is a general lack of knowledge about these initiatives and their potentials. The aim of this paper is to review current and past EU-funded projects in order to make a summary of their goals and achievements and to suggest future research needs of these European birth cohort networks. AU - Bousquet, J.* AU - Anto, J.* AU - Sunyer, J.* AU - Nieuwenhuijsen, M.* AU - Vrijheid, M.* AU - Keil, T.* AU - MeDALL Study Group (*) AU - CHICOS Study Group (*) AU - GA²LEN Study Group (*) AU - ENRIECO Consortium (Heinrich, J.) C1 - 25482 C2 - 31857 SP - 1-10 TI - Pooling birth cohorts in allergy and asthma: European Union-funded initiatives - a MeDALL, CHICOS, ENRIECO, and GA²LEN joint paper. JO - Int. Arch. Allergy Immunol. VL - 161 IS - 1 PB - Karger PY - 2013 SN - 1018-2438 ER - TY - JOUR AB - Background: Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. Methods: Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE >= 0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. Results: Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person- years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05-2.88] and the sum of allergen-specific IgEs (OR 1.18, 95% CI 1.00-1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91-1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. Conclusions: After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults. AU - Carsin, A.-E.* AU - Zock, J.P.* AU - Jarvis, D.* AU - Basagana, X.* AU - Heinrich, J. AU - Torén, K.* AU - Janson, C.* AU - Antò, J.M.* AU - Sunyer, J.* C1 - 11755 C2 - 30813 SP - 387-392 TI - Serum total immunoglobulin E is a surrogate of atopy in adult-onset asthma: A longitudinal study. JO - Int. Arch. Allergy Immunol. VL - 160 IS - 4 PB - Karger PY - 2013 SN - 1018-2438 ER - TY - JOUR AB - Sulfites are rarely suspected as causative agents of immediate-type hypersensitivity. We report on a 49-year-old male patient who developed recurrent severe hypotension after food ingestion. A diagnosis of monoclonal mast cell activation syndrome was established. In the double-blind, placebo-controlled food challenge, the patient reacted to potassium metabisulfite with anaphylaxis. AU - Cifuentes, L. AU - Ring, J.* AU - Brockow, K. C1 - 27206 C2 - 32574 SP - 94-96 TI - Clonal mast cell activation syndrome with anaphylaxis to sulfites. JO - Int. Arch. Allergy Immunol. VL - 162 IS - 1 PB - Karger PY - 2013 SN - 1018-2438 ER - TY - JOUR AB - Background: Elevated total serum immunoglobulin E (IgE) levels are a prominent feature of allergic and parasitic diseases. An epidemiologic study was conducted in East German children to describe trends in the development of total serum IgE levels and analyze the impact of potential determinants. Methods: The study consisted of three cross-sectional surveys in 1992-1993, 1995-1996 and 1998-1999 and was conducted in three areas of the former German Democratic Republic. In total, 8,051 questionnaires were completed by the parents of children aged 5-14 years, supplying information on allergic symptoms and potential risk factors. A total of 5,918 measurements of total serum IgE and specific IgE to 5 common aeroallergens were available from 4,353 schoolchildren. Generalized estimating equations were applied to data from all children and stratified for atopic and nonatopic children to identify trends and estimate the effect of potential determinants on total IgE. Results: Total serum IgE levels decreased significantly with a linear trend in East German schoolchildren between 1992 and 1999, the effect being stronger in nonatopic children. The following factors were associated with lower total serum IgE levels: female gender, living in a household with fewer than 4 people, no history of helminth infestation, younger age group (5-7 years), no parental allergy and high socioeconomic status. No association was seen for 'smoking at home' and close contact to pets. Conclusion: Total serum IgE declined parallel to helminth infestation; however, the latter explained the decrease only in part. Furthermore, total IgE developed in an opposite direction to specific IgE, indicating that it has determinants other than allergic sensitization. AU - Flohrs, K. AU - Brüske, I. AU - Thiering, E. AU - Rzehak, P. AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 7208 C2 - 29560 SP - 27-34 TI - Temporal changes in total serum immunoglobulin E levels in East German children and the effect of potential predictors. JO - Int. Arch. Allergy Immunol. VL - 158 IS - 1 PB - Karger AG PY - 2012 SN - 1018-2438 ER - TY - JOUR AB - no abstract AU - Flexeder, C. AU - Brüske, I. AU - Magnussen, H.* AU - Heinrich, J. C1 - 5939 C2 - 28417 CY - Basel SP - 117-118 TI - Association between obesity and atopy in adults? JO - Int. Arch. Allergy Immunol. VL - 156 IS - 1 PB - Karger PY - 2011 SN - 1018-2438 ER - TY - JOUR AB - Background: We have previously shown that the allergic sensitization to ovalbumin does not represent a superantigen-like immune response. In gene-targeted mice (Delta D-iD) with a single modified Diversity gene segment (D(H)) of the immunoglobulin heavy chain, enriched for charged amino acids, the asthma phenotype in a murine model was markedly alleviated compared to wild-type animals. Objective: We now sought to determine whether the confinement to a single D(H) gene segment alone leads to a reduced allergic phenotype. Methods: We examined another gene-targeted mouse strain (Delta D-DFL) with a single D(H) gene segment which encodes for neutral amino acids, thus reflecting the preferential repertoire in wild-type mice. Mice were sensitized intraperitoneally to ovalbumin. Results: Despite the constraint to a single D(H) gene segment, Delta D-DFL mice mounted high total and allergen-specific IgG(1) and IgE serum levels after sensitization to ovalbumin. The affinity constants of allergen-specific IgG(1) antibodies did not differ between Delta D-DFL and wild type. Following challenge with aerosolized allergen, a marked local T(H)2 cytokine response and an eosinophilic airway inflammation developed. Quantitative histology revealed increased mucus production and intense goblet cell metaplasia which were identical to those in wild type. Moreover, Delta D-DFL mice developed an airway hyperreactivity to methacholine and to the specific allergen, which both did not differ from those in wild-type animals. Conclusion: A single D(H) gene segment is sufficient for the establishment of the asthma phenotype in a murine model of allergic airway inflammation. Thus, the allergic phenotype depends on the amino acid composition and not on the diversity of the classical antigen-binding site. AU - Kerzel, S.* AU - Rogosch, T.* AU - Wagner, J.* AU - Preisser, K.* AU - Yildirim, A.Ö. AU - Fehrenbach, H.* AU - Garn, H.* AU - Maier, R.F.* AU - Schroeder, H.W. * AU - Zemlin, M.* C1 - 6249 C2 - 29061 SP - 247-258 TI - A single DH gene segment is sufficient for the establishment of an asthma phenotype in a murine model of allergic airway inflammation. JO - Int. Arch. Allergy Immunol. VL - 156 IS - 3 PB - Karger PY - 2011 SN - 1018-2438 ER - TY - JOUR AB - Epidemiologic studies reveal a dramatic increase in allergies in the last decades. Air pollution is considered to be one of the factors responsible for this augmentation. The aim of this study was to analyze the impact of urbanization on birch pollen. The birch pollen proteome was investigated in order to identify differences in protein abundance between pollen from rural and urban areas. The allergenicity of birch pollen from both areas was evaluated by assessing its chemotactic potency as well as its protein and allergen contents.Difference gel electrophoresis (DIGE) was used to analyze the pollen proteome. The chemotactic activity of aqueous pollen extracts was determined by migration assays of human neutrophils.RESULTS: DIGE revealed 26 differences in protein spot intensity between pollen from urban and rural areas. One of these proteins was identified by de novo sequencing as the 14-3-3 protein, which resembles a stress-induced factor in other plant species. Furthermore, extracts from pollen collected in urban areas had higher chemotactic activity on human neutrophils compared to pollen from rural sites.CONCLUSIONS: The present study points to an impact of air pollution on allergen carrier proteome and release of chemotactic substances. The increment in proinflammatory substances such as pollen-associated lipid mediators might contribute to the described urban-rural gradient of allergy prevalence. Furthermore, our study suggests that allergenicity is determined by more than the sole allergen content. AU - Bryce, M. AU - Drews, O.* AU - Schenk, M.F.* AU - Menzel, A.* AU - Estrella, N.* AU - Weichenmeier, I. AU - Smulders, M.J.* AU - Buters, J.T.M. AU - Ring, J. AU - Görg, A.* AU - Behrendt, H. AU - Traidl-Hoffmann, C. C1 - 5250 C2 - 27897 SP - 46-55 TI - Impact of urbanization on the proteome of birch pollen and its chemotactic activity on human granulocytes. JO - Int. Arch. Allergy Immunol. VL - 151 IS - 1 PB - Karger PY - 2010 SN - 1018-2438 ER - TY - JOUR AB - The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe. Methods: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios. Results: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women. Conclusions: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated. AU - Cazzoletti, L.* AU - Marcon, A.* AU - Corsico, A.* AU - Janson, C.* AU - Jarvis, D.* AU - Pin, I.* AU - Accordini, S.* AU - Bugiani, M.* AU - Cerveri, I.* AU - Gislason, D.* AU - Gulsvik, A.* AU - de Marco, R* AU - Therapy and Health Economics Group of the European Community Respiratory Health Survey (Heinrich, J. AU - Wjst, M.) C1 - 5443 C2 - 28767 CY - Basel, Switzerland SP - 70-79 TI - Asthma severity according to global initiative for asthma and its determinants: An international study. JO - Int. Arch. Allergy Immunol. VL - 151 IS - 1 PB - Karger PY - 2010 SN - 1018-2438 ER - TY - JOUR AB - The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. OBJECTIVE: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. METHODS: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. RESULTS: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). CONCLUSIONS: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably. 2007 S. Karger AG, Basel AU - Buters, J.T.M.* AU - Kasche, A.* AU - Weichenmeier, I.* AU - Schober, W.* AU - Klaus, S.* AU - Traidl-Hoffmann, C.* AU - Menzel, A.* AU - Huss-Marp, J.* AU - Krämer, U.* AU - Behrendt, H. C1 - 442 C2 - 25596 SP - 122-130 TI - Year-to-year variation in release of Bet v 1 allergen from birch pollen: Evidence for geographical differences between West and South Germany. JO - Int. Arch. Allergy Immunol. VL - 145 IS - 2 PB - Karger PY - 2008 SN - 1018-2438 ER - TY - JOUR AB - Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. MATERIAL AND METHODS: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6-96 h after allergen application and investigated immunohistochemically. RESULTS: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-gamma in the late phase. The NPT was continuously dominated by IFN-gamma. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. DISCUSSION: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase. AU - Eyerich, K. AU - Huss-Marp, J. AU - Darsow, U.* AU - Wollenberg, A. AU - Foerster, S. AU - Ring, J. AU - Behrendt, H. AU - Traidl-Hoffmann, C. C1 - 4161 C2 - 25127 SP - 213-223 TI - Pollen grains induce a rapid and biphasic eczematous immune response in atopic eczema patients. JO - Int. Arch. Allergy Immunol. VL - 145 IS - 3 PB - Karger PY - 2008 SN - 1018-2438 ER - TY - JOUR AB - Early childhood influences are important for the development of the allergic phenotype. In East Germany, tremendous lifestyle changes took place after 1990 and it can be hypothesized that the allergic phenotypes in mothers and their children are less similar than in West Germany. This was investigated in our study done in mothers and their 6-year-old children from East and West Germany in the year 2000. Methods: 1,393 mother-child pairs participated. A subgroup of 774 pairs gave blood for the determination of specific IgE. Regional differences in mother-child correlations and in prevalence of mother-child combinations with respect to allergic sensitization and disease were examined by logistic regression analysis. Results: The adjusted association in positive allergic sensitization between mothers and their children was not significant in East Germany (OR 1.23, 95% CI: 0.68-2.24) but highly significant in West Germany (OR 2.89, 95% CI: 1.73-4.80). The probability for the combination of 'negative' mother and 'positive' child was significantly higher in East than in West Germany. Conclusions: Mother-child transmission of atopy predisposition can even be cancelled by environmental changes. AU - Cramer, C.* AU - Ranft, U.* AU - Ring, J.* AU - Möhrenschlager, M.* AU - Behrendt, H. AU - Oppermann, H.* AU - Wilhelm, M.* AU - Krämer, U. C1 - 1199 C2 - 24724 SP - 282-289 TI - Allergic sensitization and disease in mother-child pairs from Germany: Role of early childhood environment. JO - Int. Arch. Allergy Immunol. VL - 143 IS - 4 PB - Karger PY - 2007 SN - 1018-2438 ER - TY - JOUR AB - Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden (n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 (95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. AU - Depner, M.* AU - Kormann, M.S.* AU - Klopp, N. AU - Illig, T. AU - Vogelberg, C.* AU - Weiland, S.K.* AU - von Mutius, E.* AU - Combadière, C.* AU - Kabesch, M.* C1 - 3790 C2 - 25007 SP - 91-94 TI - CX3CR1 polymorphisms are associated with atopy but not asthma in German children. JO - Int. Arch. Allergy Immunol. VL - 144 IS - 1 PB - Karger PY - 2007 SN - 1018-2438 ER - TY - JOUR AB - Natural allergen contact induces an increase of IgE levels and sensitivity but the mechanisms underlying the allergen-specific memory responses are poorly understood. Furthermore, it has not been studied whether allergen exposure affects the molecular reactivity profiles in patients. The aim of this study was to analyze the influence of nasal allergen encounter on the molecular profile and magnitude of memory IgE responses and on systemic sensitivity. METHODS: We investigated allergen-specific IgE, IgG subclass and IgM responses to defined allergen molecules (grass pollen: Phl p 1, Phl p 2 and Phl p 5; birch pollen: Bet v 1 and Bet v 2) in allergic patients in response to natural as well as to controlled nasal and dermal allergen exposure. Changes in systemic sensitivity were monitored by skin prick testing and by basophil histamine release experiments. RESULTS: Respiratory antigen exposure boosted IgE levels to a pre-established profile of allergen molecules without inducing significant IgM responses or new IgE specificities in allergic individuals. The importance of the route of allergen contact is demonstrated by an increase of systemic IgE levels and sensitivity after nasal exposure. In vitro sensitisation of basophils with pre- and post-seasonal serum samples suggests an allergen-induced elevation of specific IgE as a cause for the increased allergen-specific sensitivity. CONCLUSION: The characteristics of the allergen-driven antibody responses indicate a direct activation of an established pool of IgE memory cells with defined specificities as an underlying mechanism. Our finding that nasal allergen contact is a major factor for the boosting of memory IgE and systemic sensitivity may open new therapeutic possibilities. AU - Niederberger, V.* AU - Ring, J. AU - Rakoski, J. AU - Jager, S.* AU - Spitzauer, S.* AU - Valent, P.* AU - Horak, F.* AU - Kundi, M.* AU - Valenta, R.* C1 - 2395 C2 - 24735 SP - 133-144 TI - Antigens drive memory IgE responses in human allergy via the nasal mucosa. JO - Int. Arch. Allergy Immunol. VL - 142 IS - 2 PB - Karger PY - 2007 SN - 1018-2438 ER - TY - JOUR AB - Food allergy is targeted as a public health priority by the European Union Commission. Parental perception of food allergy in their offspring is a proxy measure of the potential demand for allergy medicine services in the paediatric population. METHODS: A representative sample of the general population was contacted by a randomised telephone survey in Austria, Belgium, Denmark, Finland, Germany, Greece, Italy, Poland, Slovenia and Switzerland. A standardised questionnaire was administered regarding parentally perceived food allergy reports, symptoms, foods and medical service use by their live-in children. RESULTS: 40,246 adults were polled, yielding data on 8,825 children. Parentally perceived food allergy prevalence was 4.7% (90% CI 4.2-5.2%). The most affected age group was 2- to 3-year olds (7.2%). Single-country incidence ranged between 1.7% (Austria) to 11.7% (Finland). Milk (38.5%), fruits (29.5%), eggs (19.0%) and vegetables (13.5%) were most often implicated, although with significant age-linked variations. Medical treatment was needed by 75.7% of affected children because of a food reaction. This translates into a proxy measure for food allergy prevalence of 3.75%. Skin symptoms were widespread (71.5%), followed by gastrointestinal (27.6%) and respiratory (18.5%) symptoms. DISCUSSION: We provide the first point prevalence of parentally perceived food allergy in the general paediatric population across the European Union. Parental reports confirm the public health significance of adverse reactions to some foods in specified age groups. Our data may inform intervention planning, cost of illness assessments and quality-of-life-enhancing public health measures. AU - Steinke, M.* AU - Fiocchi, A.* AU - Kirchlechner, V.* AU - Ballmer-Weber, B.* AU - Brockow, K. AU - Hischenhuber, C.* AU - Dutta, M.* AU - Ring, J. AU - Urbanek, R.* AU - Terracciano, L.* AU - Wezel, R.* AU - REDALL Study Consortium (*) C1 - 1179 C2 - 24732 SP - 290-295 TI - Perceived food allergy in children in 10 European nations. A randomised telephone survey. JO - Int. Arch. Allergy Immunol. VL - 143 IS - 4 PB - Karger PY - 2007 SN - 1018-2438 ER - TY - JOUR AU - Oldhoff, J.M.* AU - Darsow, U. AU - Werfel, T.* AU - Bihari, I.C.* AU - Katzer, K. AU - Laifaoui, J. AU - Plötz, S.G. AU - Kapp, A.* AU - Knol, E.F.* AU - Bruijnzeel-Koomen, C.A.* AU - Ring, J. AU - de Bruin-Weller, M.S.* C1 - 3741 C2 - 24231 SP - 290-294 TI - No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients. JO - Int. Arch. Allergy Immunol. VL - 141 PY - 2006 SN - 1018-2438 ER - TY - JOUR AU - Traidl-Hoffmann, C. AU - Münster, I. AU - Ring, J. AU - Behrendt, H. C1 - 2116 C2 - 23573 SP - 315-320 TI - Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: Implications for anti-inflammatory activity of antihistamines. JO - Int. Arch. Allergy Immunol. VL - 140 PY - 2006 SN - 1018-2438 ER - TY - JOUR AU - Weissenbacher, S. AU - Traidl-Hoffmann, C. AU - Eyerich, K. AU - Katzer, K. AU - Bräutigam, M.* AU - Löffler, H.* AU - Hofmann, H.* AU - Behrendt, H. AU - Ring, J.* AU - Darsow, U.* C1 - 5677 C2 - 23631 SP - 239-244 TI - Modulation of atopy patch test and skin prick test by preatment with 1% pimercrolismus cream. JO - Int. Arch. Allergy Immunol. VL - 140 PY - 2006 SN - 1018-2438 ER - TY - JOUR AB - Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria-host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed. AU - Gutermuth, J. AU - Ollert, M. AU - Ring, J.* AU - Behrendt, H. AU - Jacob, T.* C1 - 2487 C2 - 22124 SP - 262-276 TI - Mouse models of atopic eczema critically evaluated. JO - Int. Arch. Allergy Immunol. VL - 135 PY - 2004 SN - 1018-2438 ER - TY - JOUR AB - The transfer of pollen from floral anther to recipient stigma is the critical reproductive event among higher plants--this is the botanical view of pollen. Proteins and glycoproteins from pollen can function as allergens, environmental molecules interacting with the human immune system to elicit an allergic response in susceptible individuals--this is how allergists and immunologists see pollen grains. Between 10 and 25% of the population now have symptoms of hay fever or allergic asthma and the incidence has more than doubled in the past three decades while the reason(s) for this increment are only hypothetical, but there is a multitude of them. Despite our natural focus on this impact of pollen on human health, pollen have to be considered in a larger context. First of all, to evaluate the bioavailability of allergens from pollen, we have to understand their function and their influence factors. Furthermore, pollen grains are not only releasing proteins eliciting specific immune responses, but they also liberate bioactive lipid mediators and this much more rapidly. And last but not least, recent observations indicate, that pollen do not only induce allergy and thus have a much broader impact on human health. This review is an attempt to favour this holistic view of pollen and their impact on human health. AU - Traidl-Hoffmann, C. AU - Menzel, A.* AU - Jakob, T. AU - Thiel, M. AU - Ring, J. AU - Behrendt, H. C1 - 9647 C2 - 21748 SP - 1-13 TI - Impact of pollen on human health : More than allergen carriers? JO - Int. Arch. Allergy Immunol. VL - 131 IS - 1 PY - 2003 SN - 1018-2438 ER - TY - JOUR AB - Background: The ENU Mouse Mutagenesis Project aims at a large-scale, systematic production of mouse mutants using the alkylating agent ethyl-nitrosourea (ENU). Offspring of mutagenized mice are subjected to a multiparameter screen to detect alterations in various phenotypes with the ultimate goal of identifying novel genes relevant for the expression of the phenotype. Using this approach, we have analyzed plasma IgE concentrations to identify mouse mutants with aberrant plasma IgE levels. Methods and Results: ENU-mutagenized male C3HeB/FeJ were mated to wild-type females to produce F1 offspring. F1 animals were analyzed for alterations in their plasma IgE concentrations that showed a dominant mode of inheritance, or bred further to screen for recessive phenotypes. Plasma IgE concentrations were deter mined by ELISA and a normal range for plasma IgE was established using C3HeB/FeJ wild-type animals. So far we have tested 6568 F1 animals. Repeated testing confirmed a stable aberrant IgE phenotype in 124 animals. To confirm the genetic basis of the observed phenotype, these mice were subjected to confirmation crossing. Currently we have established 9 independent m uta nt mouse lines (3 with high plasma IgE and 6 with plasma IgE below detection limit) that have been genetically confirmed and additional 24 variant mouse lines are currently undergoing confirmation testing. Conclusion: ENU mouse mutagenesis allowed us to generate and identify mouse mutants with aberrant plasma IgE levels, which may be used to characterize novel genes involved in IgE regulation and may serve as animal models for IgE-mediated diseases. AU - Alessandrini, F.* AU - Jakob, T.* AU - Wolf, A.* AU - Wolf, E.* AU - Balling, R. AU - Hrabě de Angelis, M. AU - Ring, J.* AU - Behrend, H.* C1 - 21743 C2 - 19923 SP - 25-28 TI - ENU Mouse Mutagenesis : Generation of Mouse Mutants with Aberrant Plasma IgE Levels. JO - Int. Arch. Allergy Immunol. VL - 124 PY - 2001 SN - 1018-2438 ER - TY - JOUR AU - Behrendt, H. AU - Kasche, A. AU - Ebner von Eschenbach, C. AU - Risse, U. AU - Huss-Marp, J. AU - Ring, J.* C1 - 21853 C2 - 20069 SP - 121-125 TI - Secretion of Proinflammatory Eicosanoid-Like Substances Precedes Allergen Release from Pollen Grains in the Initiation of Allergic Sensitization. JO - Int. Arch. Allergy Immunol. VL - 124 PY - 2001 SN - 1018-2438 ER - TY - JOUR AB - Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces large amounts of interleukin-5. In this study, we examined 60 patients with idiopathic eosinophilia. Sixteen patients had circulating T cells with an aberrant immunophenotype that, in most cases, were associated with different forms of skin inflammation. The abnormal T cells produced large amounts of interleukin-5, which may have increased eosinophil differentiation in the bone marrow of these patients. AU - Simon, H.-U.* AU - Plötz, S.G. AU - Simon, D.* AU - Dummer, R.* AU - Blaser, K.* C1 - 22113 C2 - 20791 SP - 242-245 TI - Clinical and Immunological Features of Patients with Interleukin-5-Producing T Cell Clones and Eosinophilia. JO - Int. Arch. Allergy Immunol. VL - 124 IS - 1-3 PY - 2001 SN - 1018-2438 ER -