Allergy | EPFL Graph Search

Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions. Common allergens include pollen and certain foods. Metals and other substances may also cause such problems. Food, insect stings, and medications are common causes of severe reactions. Their development is due to both genetic and environmental factors. The underlying mechanism involves immunoglobulin E antibodies (IgE), part of the body's immune system, binding to an allergen and then to a receptor on mast cells or basophils where it triggers the release of

Novel Analytical Methods for Allergy-Related Studies

Mikaël Frossard

Managing and treating diseases require a deep understanding of the pathologies coupled with accurate diagnostic procedures. The constant development and improvement of bioanalytical methods reflect the need of diagnosis ameliorations with respect to accuracy, sensitivity and efficiency. The field of allergy diagnosis is a good example. Despite affecting almost a third of the population in western countries, allergies still present complex challenges for the physicians in terms of diagnosis and allergen characterization. This thesis presents novel analytical methods developed for the fast and personalized allergy component-resolved diagnosis (CRD), the allergen identification and quantification in food matrices and the characterization of allergen modifications, notably nitration. Immunomagnetic separation (IMS) was used to perform the allergy diagnosis at the molecular level by extracting the IgE antibodies from allergic patient blood sera and probing them against individual allergens and natural allergenic extracts. The fast and highly selective IMS procedure was coupled to matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometry (MS) to identify accurately and with high sensitivity the proteins recognized as sensitizers by the patient antibodies. The developed CRD methods were successful to diagnose cowâs milk, egg, peanut and tree nuts allergies, allowing the resolution of several complex clinical cases. Additionally, precious information was collected for the cross-reactivity and cross-sensitization in peanut and tree nuts allergies using blood sera from the PronNut clinical study. Allergen nitration is one of the potential causes for the increase in allergy prevalence observed recently and requires thorough investigation. Herein, various nitrating agents were tested and compared for in vitro allergen nitration. After modifying allergens using two of the most efficient nitrating procedures, the nitration sites were identified by bottom-up proteomics (BUP) and compared to the known epitopes, bringing useful information and novel insights to the problem of correlation between protein nitration and allergenicity. The presence of a minute amount of allergens in a food product is responsible for potential life-threatening reactions in highly allergic patients and sensitive analytical methods are therefore required in food quality assessments. A proteomic-based method was used for the quality control of several food products suspected of causing severe reactions for peanut and hazelnut-allergic patients. Peptide markers were identified in a first screening of the food extracts by BUP using a high-resolution MS instrument. A standard addition method was then used to quantify peanut and hazelnut proteins by BUP using an untargeted âshotgunâ approach.

EPFL2020

Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis

Eva Sabrina Gollwitzer, Nicola Harris, Benjamin John Marsland

Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.

Nature Publishing Group2014

Dysregulation of Allergic Airway Inflammation in the Absence of Microbial Colonization

Nicola Harris, Tina Herbst, Benjamin John Marsland

RATIONALE: The incidence of allergic disorders is increasing in developed countries and has been associated with reduced exposure to microbes and alterations in the commensal bacterial flora. OBJECTIVES: To ascertain the relevance of commensal bacteria upon the development of an allergic response, we utilized a model of allergic airway inflammation in germ-free (GF) mice that lack any exposure to pathogenic or non-pathogenic microorganisms. METHODS: Allergic airway inflammation was induced in GF, specific pathogen free (SPF) or recolonized mice by sensitization and challenge with ovalbumin (OVA). The resulting cellular infiltrate and cytokine production were measured. MEASUREMENTS AND MAIN RESULTS: Our results show that the total number of infiltrating lymphocytes and eosinophils were elevated in the airways of allergic GF mice as compared to control SPF mice, and that this increase could be reversed by re-colonization of GF mice with the complex commensal flora of SPF mice. Exaggerated airway eosinophilia correlated with increased local production of Th2 associated cytokines, elevated IgE production and an altered number and phenotype of conventional dendritic cells (cDC). Regulatory T cell populations and regulatory cytokine levels were unaltered but GF mice exhibited an increased number of basophils and decreased numbers of alveolar macrophages (AM) and plasmacytoid dendritic cells (pDC). CONCLUSIONS: These data demonstrate that the presence of commensal bacteria is critical for ensuring normal cellular maturation, recruitment and control of allergic airway inflammation.

2011

Novel Analytical Methods for Allergy-Related Studies

Mikaël Frossard

EPFL2020