Center for Allergy and Environment

München, Germany

Center for Allergy and Environment

München, Germany
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Pichler U.,Christian Doppler Laboratory | Hauser M.,Christian Doppler Laboratory | Wolf M.,Christian Doppler Laboratory | Bernardi M.L.,Centers for Molecular Allergology | And 15 more authors.
PLoS ONE | Year: 2015

Background Pollen released by allergenic members of the botanically unrelated families of Asteraceae and Cupressaceae represent potent elicitors of respiratory allergies in regions where these plants are present. As main allergen sources the Asteraceae species ragweed and mugwort, as well as the Cupressaceae species, cypress, mountain cedar, and Japanese cedar have been identified. The major allergens of all species belong to the pectate lyase enzyme family. Thus, we thought to investigate cross-reactivity pattern as well as sensitization capacities of pectate lyase pollen allergens in cohorts from distinct geographic regions. Methods The clinically relevant pectate lyase pollen allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen extracts, and patients' sensitization pattern of cohorts from Austria, Canada, Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments. Moreover, we performed microarray experiments and established a mouse model of sensitization. Results In ELISA and ELISA inhibition experiments specific sensitization pattern were discovered for each geographic region, which reflected the natural allergen exposure of the patients. We found significant cross-reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens, which was however limited between the orders. Animal experiments showed that immunization with Asteraceae allergens mainly induced antibodies reactive within the order, the same was observed for the Cupressaceae allergens. Cross-reactivity between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in general higher immunogenicity. Conclusion We could cluster pectate lyase allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1, respectively, at which each category has the potential to sensitize predisposed individuals. The sensitization pattern of different cohorts correlated with pollen exposure, which should be considered for future allergy diagnosis and therapy. © 2015 Pichler et al.


Darsow U.,TU Munich | Darsow U.,Center for Allergy and Environment | Wollenberg A.,Ludwig Maximilians University of Munich | Simon D.,University of Bern | And 12 more authors.
World Allergy Organization Journal | Year: 2013

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. "Eczema school" educational programs have been proven to be helpful. © 2013 Darsow et al.; licensee BioMed Central Ltd.


Darsow U.,Center for Allergy and Environment | Darsow U.,TU Munich | Fedorov M.,Center for Allergy and Environment | Fedorov M.,TU Munich | And 8 more authors.
Contact Dermatitis | Year: 2012

Background. Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis. Methods. We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods. Results. A nickel detection limit of 0.2 μg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 μg/l (age 18-30 years) and 3.98 μg/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls. Conclusions. The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 μg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy. © 2012 John Wiley & Sons A/S.


Cramer C.,Iuf Institute For Umweltmedizinische Forschung | Link E.,Iuf Institute For Umweltmedizinische Forschung | Horster M.,Iuf Institute For Umweltmedizinische Forschung | Koletzko S.,Ludwig Maximilians University of Munich | And 16 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010

Background: Several studies showed a protective effect of elder siblings on eczema development, which is in line with the hygiene hypothesis. However, findings are not consistent, and there might exist different causal pathways for the development of eczema. Especially barrier disturbances as found in children with mutations in the filaggrin gene (FLG) seem to play an important role. Objectives: To investigate the interaction between FLG mutations and the presence of elder siblings on the development of eczema in 2 independent birth cohorts. Methods: We used data from 2 German birth cohorts (LISAplus, GINIplus) up to the age of 6 years. Genotyping for FLG mutations (R501X, 2282del4) was performed in 1039 (LISAplus) and 1828 (GINIplus) children. Data on eczema (diagnosis and symptoms) and elder siblings were obtained by parental questionnaires. The association among eczema, FLG mutations, and elder siblings was analyzed longitudinally by using generalized estimating equations. Results: We found no protective effect of elder siblings on eczema development. On the contrary, children with FLG mutations had a significantly higher risk for eczema if they had elder siblings. Attending day care centers lessened this effect. After excluding 303 children who attended early day care, the odds ratio for interaction between FLG mutations and elder siblings was 3.27 (95% CI, 1.14-9.36) in LISAplus and 2.41 (95% CI, 1.06-5.48) in GINIplus. Conclusion: Our findings did not confirm a protective sibling effect. The prevalence of eczema in children with filaggrin deficiency was higher if elder siblings were present. Our results give evidence for complex skin-driven pathogenic mechanisms that might be different depending on children's genetic backgrounds. © 2010 American Academy of Allergy, Asthma & Immunology.


Alessandrini F.,TU Munich | Alessandrini F.,Helmholtz Center for Environmental Research | Weichenmeier I.,TU Munich | Weichenmeier I.,Center for Allergy and Environment | And 11 more authors.
Particle and Fibre Toxicology | Year: 2010

Background: Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation.Methods: Ovalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 μg/m3for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-α mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations.Results: In non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-α relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells.Conclusion: Our findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation. © 2010 Alessandrini et al; licensee BioMed Central Ltd.


Hausteiner C.,TU Munich | Hausteiner C.,Helmholtz Center Munich | Hausteiner C.,University of Hamburg | Hausteiner C.,Center for Allergy and Environment | And 52 more authors.
Journal of Psychosomatic Research | Year: 2010

Objective: Psychobehavioral characteristics of patients with somatoform disorders (SFDs), are increasingly discussed as possible positive criteria for this diagnostic group. However, little is known about psychobehavioral differences, or similarities, between the different SFD presentations, i.e., polysymptomatic [multisomatoform/somatization disorders (MSD)] versus mono- or oligosymptomatic courses [pain disorder (PD), undifferentiated somatoform disorder (USD)]. Methods: This is a cross-sectional study including 268 consecutive allergology inpatients. After an Structured Clinical Interview for DSM-IV, patients completed several self-rating questionnaires. Results were compared within the different SFD presentations as well as between patients with versus without SFDs. Results: We identified 72 patients with an SFD. There were fewer and smaller psychobehavioral differences within patients with the different SFD presentations (MSD, USDs, PDs) than between patients with undifferentiated versus no SFD. Patients with one of the three different SFD subdiagnoses scored similarly on many measures referring to psychosocial distress (e.g., psychological distress, mental health-related quality of life, dissatisfaction with care). The number of reported symptoms, somatic symptom severity, a self-concept of bodily weakness, the degree of disease conviction, and physical health-related quality of life discriminated the different SFD presentations not only from patients without SFDs but also from each other. Conclusions: Patients diagnosed with one of the different SFD subtypes share many psychobehavioral characteristics, mostly regarding the reporting of psychosocial distress. Perceived somatic symptom severity and physical impairment as indicators of bodily distress could either further define categorical subdivisions of SFD or dimensionally graduate one general SFD category defined by bothering bodily symptoms and disproportionate psychosocial distress. © 2010 Elsevier Inc.


Eyerich K.,Center for Allergy and Environment | Eyerich S.,Center for Allergy and Environment | Hiller J.,Center for Allergy and Environment | Behrendt H.,Center for Allergy and Environment | And 2 more authors.
European Journal of Dermatology | Year: 2010

Chronic mucocutaneous candidiasis (CMC) defines a heterogeneous group of orphan and inherited syndromes characterised by chronic and recurrent infections of the skin and mucosa with the yeast Candida. Increasing evidence suggests that this inefficient defence against Candida species is reflected by a DC/T cell defect which results in an impaired Th17 and Th1 immune response and, consecutively, a failed immune instruction of tissue cells. Little is known about the incidence and prognosis of CMC. Clinically, the main complications are debilitating hands (Candida granuloma) and oesophageal stricture with potential mal-digestion/-absorption. Furthermore, the chronic infections are likely a risk factor for the development of squamous cell carcinoma. Since resistance to anti-mycotic drugs evolves rapidly, efficient and flexible therapeutic management is essential for CMC patients.


PubMed | Center for Allergy and Environment
Type: | Journal: Chemical immunology and allergy | Year: 2014

It may be a coincidence, but it is a fact that the first clear characterization of hay fever began in England where modern industrialization started in Europe. Only at the end of the 20th century were associations of the increasing prevalence of allergy with outdoor air pollution discussed. The seminal study came from Japan from the group of T. Miyamoto linking the increase in Japanese cedar pollinosis to an increased prevalence of Diesel cars and probably exposure to Diesel exhaust in epidemiological, animal experimental and in vitro studies. In Germany first epidemiological studies were done in North Rhine-Westphalia and Bavaria in 1987 and 1988 showing a striking prevalence of allergic disease of up to 10-20% in preschool children. After German reunification the most surprising observation was a lower prevalence of hay fever in East German children compared to the West, although there was a much higher air pollution with SO2 and large particulate matter. Modern smog as found over West German cities most likely originating from traffic exhaust and consisting of fine and ultrafine particles was shown to be associated with higher incidence rates of allergy and allergic sensitization. In the 10 years after reunification there was a steep increase of allergy prevalence in East German children reaching almost the same level as in West Germany. Obviously, a multitude of lifestyle factors - beyond air pollution - may be involved in the explanation of this phenomenon. Surprisingly the skin manifestation of atopy, namely atopic eczema, was more frequent in East German children compared to the West, thus differing from airway allergy. Meanwhile in vitro studies and animal experiments have shown that a variety of air pollutants mostly from environmental tobacco smoke (indoors) and from traffic exhaust (outdoors) can stimulate immune cells inducing a Th2-dominated response besides their irritative effects. While 50 years ago in allergy textbooks a clear distinction was made between toxic or allergic, the newly developed concept of allergotoxicology has stimulated research tremendously, meaning the investigation of effects of toxic substances upon the induction, elicitation and maintenance of allergic reactions.


PubMed | Center for Allergy and Environment
Type: Journal Article | Journal: European journal of dermatology : EJD | Year: 2010

Chronic mucocutaneous candidiasis (CMC) defines a heterogeneous group of orphan and inherited syndromes characterised by chronic and recurrent infections of the skin and mucosa with the yeast Candida. Increasing evidence suggests that this inefficient defence against Candida species is reflected by a DC/T cell defect which results in an impaired Th17 and Th1 immune response and, consecutively, a failed immune instruction of tissue cells. Little is known about the incidence and prognosis of CMC. Clinically, the main complications are debilitating hands (Candida granuloma) and oesophageal stricture with potential mal-digestion/-absorption. Furthermore, the chronic infections are likely a risk factor for the development of squamous cell carcinoma. Since resistance to anti-mycotic drugs evolves rapidly, efficient and flexible therapeutic management is essential for CMC patients.


PubMed | Center for Allergy and Environment
Type: Journal Article | Journal: Contact dermatitis | Year: 2012

Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis.We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods.A nickel detection limit of 0.2 g/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 g/l (age 18-30 years) and 3.98 g/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls.The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 g/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.

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