Research Margo Hagendorens

Abstract

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that occurs in about 20% of children and 3% of adults in Western countries. AD is characterized by acute flare-ups of itchy eczematous lesions and dry skin. The etiology of AD is complex, the appearance and course of the disease are influenced by both genetic and immunological mechanisms and environmental factors, such as pathogenic microorganisms. In this project,, we aim to characterize the microbiome of children with AD and investigate the impact of a topical therapeutic strategy with well selected lactobacilli.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Hagendorens Margo
• Fellow: Delanghe Lize

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Increasing lines of evidence indicate that mast cells (MC) degranulation from off-target occupation of the Mas-related G protein coupled receptor X2 (MRGPRX2) constitutes a novel endotype of IgE/FcεRI (high affinity receptor for IgE) -independent drug anaphylaxis. However, most of the data have been gathered in mice or in malignant mast cell lines. In contrast to MC, MRPGPRX2 is barely expressed on basophils membrane but quickly upregulated after conditioning. Here we propose exploration of a mixed model based upon cultured human mast cells and human basophils aiming at deciphering MRGRPX2 agonism and antagonims in drug anaphylaxis.

Researcher(s)

• Promoter: Sabato Vito
• Co-promoter: Ebo Didier
• Co-promoter: Hagendorens Margo
• Fellow: Van der Poorten Marie-Line

Research team(s)

• Immunology

Project type(s)

• Research Project

Abstract

Unverified and allergies to penicillins have developed into an epidemic with unacceptable medical and financial consequences. For over two decades numerous efforts have been undertaken to fight this scourge and to promote judicious diagnosis to reduce erroneous avoidance and unnecessary substitutions with less effective, more toxic and costly broad spectrum second-line non-betalactam antibiotics carrying the potential of the emergence of organism resistance and secondary complications. However, old habits die hard and continuous efforts are required to convince patients and their physicians of the consequences of these false allegations and to encourage implementation of correct management protocols. In this project we primarily aim at i) mapping out the prevalence of spurious and genuine penicillin allergy, ii) optimizing diagnostic management of betlactam allergies according to the individual allergy risk status including resolving the conundrum of cross-reactivity between penicillin and other belactams and iii) evaluate the cost-effectiveness of delabelling spurious "penicillin allergy" in unselected or selected populations. Altogether, our data should facilitate introduction of a cost-effective diagnostic and therapeutic algorithms without jeopardizing health of our patients and benefiting antibiotic stewardship.

Researcher(s)

• Promoter: Sabato Vito
• Co-promoter: Hagendorens Margo

Research team(s)

• Immunology

Project type(s)

• Research Project

Abstract

IgE-mediated peanut allergy starts with a sensitization phase that is characterized by the production of peanut specific IgE (sIgE) antibodies that can be depicted by peanut immunoassays and/or skin tests. However, the production of these peanut sIgE antibodies is not sufficient for the development of an overt peanut allergy. Actually, many subjects with detectable peanut sIgE antibodies in their serum and/or positive skin test response to peanut do not exhibit clinical manifestations when consuming this legume. The divergence between allergic sensitization and clinically overt allergy not only poses significant diagnostic difficulties but also constitutes a fundamental gap in our knowledge and insights about the complex mechanisms of food allergy and tolerance. Clearly, in prospect for future therapy, better understanding of the underlying (molecular) mechanisms is needed. In this project I will investigate whether the clinical phenotype of peanut sensitization and allergy results from altered basophil responses to stimulation with peanut. More specifically, I will look for alterations in basophilic expression and/or function of three families of functionally distinctive inhibitory receptors, i.e. CD300a, CD32B and Siglec-7, 8 and 9. Obtaining more fundamental insights in the basophil response, may disclose diagnostic but also potential therapeutic targets that have already shown promising preclinical results for various mast cell and basophil associated conditions.

Researcher(s)

• Promoter: Ebo Didier
• Co-promoter: Hagendorens Margo
• Co-promoter: Sabato Vito
• Fellow: Van Gasse Athina

Research team(s)

• Immunology

Project type(s)

• Research Project

Abstract

Nonspecific-lipid transfer proteins (ns-LTPs) have increasingly been recognized to constitute a significant cause of plant food allergy. Sensitization to ns-LTPs was predominantly observed in adults and appeared mainly associated with severe generalized reactions. However, we established that in northern Europe sensitization to ns-LTP can also occur in children and that the sensitization profile assessed by quantification of specific IgE antibodies is not predictive for the clinical phenotype. We hypothesize that a more functional approach with basophil activation experiments (BAT) could be of better predictive value to ascertain the clinical relevance of a sensitization to ns-LTP, as basophil activation requires cross-linking of IgE/FcεRI complexes and therefore more closely mirrors the in vivo situation. We aim at deciphering the clinical relevance of a sensitization to two ns-LTP, i.e. Pru p 3 from peach (Prunus persica) and Mal d 3 (Malus domesticus) from apple, by applying basophil activatation experiments, which might enter mainstream diagnostics as an instrument to discriminate between clinical relevant and irrelevant ns-LTP sensitization. Additionally, the functional activity of so-called blocking IgG4 antibodies will be evaluated.

Researcher(s)

• Promoter: Hagendorens Margo

Research team(s)

• Immunology
• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project website

Project type(s)

• Research Project

Abstract

IgE-mediated peanut allergy starts with a sensitization phase that is characterized by the production of peanut specific IgE (sIgE) antibodies that can be depicted by peanut immunoassays and/or skin tests. However, the production of these peanut sIgE antibodies is not sufficient for the development of an overt peanut allergy. Actually, many subjects with detectable peanut sIgE antibodies in their serum and/or positive skin test response to peanut do not exhibit clinical manifestations when consuming this legume. The divergence between allergic sensitization and clinically overt allergy not only poses significant diagnostic difficulties but also constitutes a fundamental gap in our knowledge and insights about the complex mechanisms of food allergy and tolerance. Clearly, in prospect for future therapy, better understanding of the underlying (molecular) mechanisms is needed. In this project I will investigate whether the clinical phenotype of peanut sensitization and allergy results from altered basophil responses to stimulation with peanut. More specifically, I will look for alterations in basophilic expression and/or function of three families of functionally distinctive inhibitory receptors, i.e. CD300a, CD32B and Siglec-7, 8 and 9. Obtaining more fundamental insights in the basophil response, may disclose diagnostic but also potential therapeutic targets that have already shown promising preclinical results for various mast cell and basophil associated conditions.

Researcher(s)

• Promoter: Ebo Didier
• Co-promoter: Hagendorens Margo
• Co-promoter: Sabato Vito
• Fellow: Van Gasse Athina

Research team(s)

• Immunology

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Ebo Didier
• Co-promoter: Hagendorens Margo
• Co-promoter: Stevens Wim

Research team(s)

Project type(s)

• Research Project

Abstract

The primary objective of the project is to investigate and validate the Basophil activation test in the diagnosis of class II food allergy and to identify patients with definite food allergies. Furthermore, the technique will be applied to discriminate between clinically relevant and irrelevant sIgE antibody results.

Researcher(s)

• Promoter: Stevens Wim
• Co-promoter: Ebo Didier
• Co-promoter: Hagendorens Margo

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Stevens Wim
• Co-promoter: Berneman Zwi
• Co-promoter: De Clerck Luc
• Co-promoter: Ebo Didier
• Co-promoter: Hagendorens Margo
• Co-promoter: Van Tendeloo Vigor

Research team(s)

Project type(s)

• Research Project