Research team

Immunology

Expertise

Immune evaluation. Functional tests : basophil activation test, phagocytosis, chemotaxis, cytotoxicity.

IgE-independent drug-induced anaphylaxis, MRGPRX2, basophils and mast cells: connecting the dots. 01/10/2018 - 30/09/2023

Abstract

Anaphylaxis is a potentially life-threatening generalized reaction in which degranulation of basophils and mast cells (MC) is critical. Anaphylaxis can result from allergen that cross-links specific IgE bound to the membrane of the effector cells. This cross-linking of IgE initiates downstream signalling with release of vasoactive mediators (e.g. histamine), along with preformed proteases and cytokines, and de novo synthesis and secretion of lipid mediators and additional cytokines. However, evidence has accumulated that anaphylaxis can also occur in response to IgEindependent stimuli, including occupation of the Mas-related G protein-coupled receptor MRGPRX2. Although quintessence of these studies appears to indicate off-target occupancy of the MRGPRX2 receptor to constitute a novel non-immune endotype of MC-driven drug anaphylaxis, prudence is called upon interpretation of the findings as data in patients are lacking. We will take advantage of our experience in studying mechanisms governing basophil and mast cell activation/degranulation to unveil the processes after MRGPRX2-related anaphylaxis to drugs. Flow-assisted quadruple analysis of activation markers, inhibition receptors, signalling molecules and mediator release by individual human cells will capture data that are inaccessible in animal models or by traditional techniques requiring homogeneous cell populations and of which results only represent an average of all stimulated cells.

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  • Immunology

Role of inhibitory receptors in piecemeal and anaphylactic degranulation of basophils and mast cells. 01/10/2013 - 30/09/2018

Abstract

In this project we will continue and extend our explorations of activation markers, inhibitory receptors, signalling molecules and release of mediators such as histamine that was initiated in FWO project 1800609N. Our purpose is to further explore and disentangle the mechanisms that regulate piecemeal and anaphylactic degranulation of basophils and mast cells. In addition we will explore the mechanisms that could account for temporarily (allergenspecific) hypo- and unresponsiveness of both cells.

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    Anaesthesia-related allergy: from new insights in pathomechanisms to reliable diagnostic instruments. 01/10/2013 - 30/09/2017

    Abstract

    Allergy during anaesthesia is an important health problem with a significant mortality and morbidity. Unfortunately, correct diagnosis is not always straightforward and too frequently overlooked. As a consequence, patients are at unnecessary risk for future life-threatening reactions. Uncertainties associated with skin testing using some of these drugs and the general unavailability of drug-specific immunoglobulin E tests contribute to the frequent failure of adequate investigation and identification of underlying mechanisms, distinguishing IgE-independent from IgE-dependent true anaphylactic reactions in these patients. In this project we would like to explore further the underlying pathomechanisms of immediate type (or IgE-mediated) hypersensitivity reactions that occur during general anaesthesia. For this purpose, we will take opportunity of having developed and validated up-to-date flow cytometric techniques like basophil activation tests and a cellular histamine content assay (HistaFlow®: patented by our laboratory) next to recently developed tools to culture mast cells out of circulating CD34+ progenitor cells. This will enable a combined analysis of surface markers and histamine release after IgE-dependent and IgE-dependent basophil and mast cell activation. Moreover, by having set in place a reference centre with highest throughput of patients in Belgium, it is anticipated that these experiments not only might culminate in the development of novel diagnostic tests to document drug hypersensitivity reactions, but also might help to define save anaesthetic alternatives.

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      Influence of therapy on T cell signal transduction in Th1 and Th2 type diseases. 01/10/2008 - 30/09/2010

      Abstract

      The aim of the project is to study the role of intracellular signalling molecules in T helper cell differentiation in patients with rheumatoid arthritis (as a model of T helper 1-mediated disease) and wasp venom allergy (Th2). Relevant signalling molecules include STAT4, STAT5, STAT6 and p38 MAPK. Using a cell-based technique, the effect of stimuli from dendritic cells and regulatory T cells on the activation of cell signalling is studied, as well as the effect of therapy that is known to induce a clinically "tolerant" state.

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        Influence of therapy on T cell signal transduction in Th1 en Th2 type diseases. 01/10/2006 - 30/09/2008

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          Study of in vivo and in vitro modulation of dendritic cells in Th1 (rheumatoid arthritis) and Th2 (venom allergy) mediated diseases. Influence of anti-TNF and immunotherapy. 01/01/2006 - 31/12/2009

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            01/06/2002 - 31/12/2004

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              Study of cord blood monocytes in neonates of atopic and non-atopic parents. 01/06/2002 - 31/12/2002

              Abstract

              It is postulated that cord blood monocytes from neonates of atopic parents have different features than monocytes from newborns ofnon-atopic parents. Our hypothesis will be evaluated at two levels. After incubation with antigens, the secretion of cytokins and PGE2 by cord blood monocytes will be assessed. Further the influence of primed monocytes on the lymphocytic immune response will be determined by evaluating T -cell proliferation and production of cytokines by T -lymphocytes.

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                Influence of immune complexes on chondrocyte apoptosis in rheumatoid arthritis. 01/01/2002 - 31/12/2004

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                  01/01/2001 - 31/05/2002

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                    Type 1 and type 2 cytokine profile of T-helper Iymphocytes and T-cytotoxic/suppressor lymphocytes of allergic patients (asthma, atopic dermatitis, hymenoptera anaphylaxis) and of patients with rheumatoid arthritis. 01/10/2000 - 30/09/2002

                    Abstract

                    T-helper cells are divided into T-helper 1 (Th1 ) and T-helper 2 cells (Th2), based on the different secretion of cytokines. Th1 cells produce especially interleukin-2 (IL-2) and interferon-gamma (IFNy). Th2 cells produce cytokines like IL-4, IL-5, IL-10 en IL-13. By the analogy with T-helper (CD4+) cells, T-cytotoxic/suppressor (CD8+) cells are divided into two subpopulations, that have a similar functional heterogeneity: Tc1 and Tc2 cells. Th 1 cells are important in the evolution and pathogenesis auto-immune diseases such as rheumatoid arthritis. On the other hand, allergic patients show a Th2 cytokine profile. In this study, the influence of disease activity and therapeutic interventions on cytokine profiles of allergie patients (atopic dermatitis, allergie asthma, hymenoptera anafylaxis) and of rheumatoid arthritis patients is investigated.

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                      Influence of immune complexes on chondrocyte function in rheumatoid arthritis 01/01/2000 - 31/12/2002

                      Abstract

                      In this project, the influence of immune complexes on chondrocyte functions will be studied in rheumatoid arthritis. Immune complexes are present in serum, synovial fluid and superficial layers of cartilage of rheumatoid arthritis patients. Experimental data in animals suggest that immune complexes provoque cartilage destruction. However data in man are lacking. Parameters of chondrocyte function that will be investigated include chondrocyte growth, production of inflammatory mediators, necrosis and apoptosis.

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                        Study of cord blood monocytes in neonates of atopic and non-atopic parents. 01/01/2000 - 31/05/2002

                        Abstract

                        It is postulated that cord blood monocytes from neonates of atopic parents have different features than monocytes from newborns of non-atopic parents. Our hypothesis will be evaluated at two levels. After incubation with antigens, the secretion of cytokins and PGE2 by cord blood monocytes will be assessed. Further the influence of primed monocytes on the lymphocytic immune response will be determined by evaluating T-cell proliferation and production of cytokines by T-lymphocytes.

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                          Thrombin generation and thrombosis - importance of genetic and immune phenomena, value of pharmacological interventions. 21/12/1998 - 22/12/2001

                          Abstract

                          This project will study 4 main topics : 1. autoantibodies in thrombotic events; 2. impact of fibronolytics on thrombin generation, contact and complement activation; 3. effect of antiplatelet and lipid-lowering drugs and nutrition supplementation on thrombin generation; 4. genetic aspects of thrombophilia.

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                            Type 1 and type 2 cytokine profile of T-helper Iymphocytes and T-cytotoxic/suppressor lymphocytes of allergic patients (asthma, atopic dermatitis, hymenoptera anaphylaxis) and of patients with rheumatoid arthritis. 01/10/1998 - 30/09/2000

                            Abstract

                            T-helper cells are divided into T-helper 1 (Th1 ) and T-helper 2 cells (Th2), based on the different secretion of cytokines. Th1 cells produce especially interleukin-2 (IL-2) and interferon-gamma (IFNy). Th2 cells produce cytokines like IL-4, IL-5, IL-10 en IL-13. By the analogy with T-helper (CD4+) cells, T-cytotoxic/suppressor (CD8+) cells are divided into two subpopulations, that have a similar functional heterogeneity: Tc1 and Tc2 cells. Th 1 cells are important in the evolution and pathogenesis auto-immune diseases such as rheumatoid arthritis. On the other hand, allergic patients show a Th2 cytokine profile. In this study, the influence of disease activity and therapeutic interventions on cytokine profiles of allergie patients (atopic dermatitis, allergie asthma, hymenoptera anafylaxis) and of rheumatoid arthritis patients is investigated.

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                              Influence of biphosphonates on corticosteroid-induced osteoporosis in rheumatoid arthritis. 01/10/1996 - 31/12/1998

                              Abstract

                              The influence of bisphosphonates on the bone mineral content and biological parameters of osteoporosis is investigated in patients with rheumatoid arthritis treated with low dose prednisolone. The in vitro modification of production of inflammatory cytokines (Tumor necrosis factor, interleukin-1 and -6) by monocytes is studied.

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                                Study of cord blood lymphocytes as a prediction of atopic disorders (asthma and atopic dermatitis). 01/01/1996 - 31/12/1999

                                Abstract

                                The aim of the project is to study cord blood lymphocytes of an unselected group of neonates; the children have to be born after an uncomplicated pregnancy and a normal birth. All children will be followed during the first two years of life with special attention to the development of asthma and atopic dermatitis. The purpose is to look if cord blood lymphocytes of subsequently atopic children have other features than cord blood lymphocytes of normal children.

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                                  Study of cord blood lymphocytes as a prediction of atopic disorders (asthma and atopic dermatitis). 01/01/1996 - 31/12/1996

                                  Abstract

                                  The aim of the project is to study cord blood lymphocytes of an unselected group of neonates; the children have to be born after an uncomplicated pregnancy and a normal birth. All children will be followed during the first two years of life with special attention to the development of asthma and atopic dermatitis. The purpose is to look if cord blood lymphocytes of subsequently atopic children have other features than cord blood lymphocytes of normal children.

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                                    The role of exposure to silica in ANCA-associated glomerulonephritides. 01/01/1995 - 31/12/1997

                                    Abstract

                                    This study, aiming to study the association between occupational exposure to silicon-containing compounds and the development of ANCA-positive glomerulonephritis, consists in 4 interdependent parts. A case-control study will determine the risk ratio of nephrotoxicity after silica- exposure. In a toxicological part, broncho-alveolar lavage fluid will be investigated. During a chemical analysis, the identificatian/specification of the silicon particle will be studied. A experimental part aims to obtain more insight in the pathophysiological mechanism using a ratmodel with inhalation of silica particles.

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                                      Role of exposure to and inhalation of silicon compounds in ANCA-associated glomerulonephritis. 01/01/1995 - 31/12/1995

                                      Abstract

                                      In the project the (1) relationship between the exposure to silicon compounds and the prevalence of ANCA-positive glomerulonephritis (2) the value of BAL for the evaluation of exposure to silicon compounds (3) the type and the composition of silicon compounds in the working environment responsible for the development of ANCA's be investigated and an experimental rat model be developed.

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                                        Leucocyte adhesion and interaction with endothelium and cartilage in rheumatoid arthritis 01/10/1992 - 30/09/1996

                                        Abstract

                                        In this project on rheumatoid arhtritis, an important initial step in the inflammatory proces, i.e. the adhesion of leukocytes to endothelium, is studied. Adhesive properties of neutrophils and eosinophils are compared. Furthermore, on cartilage level, the adhesion and interaction of granulocytes and chondrocytes is investigated.

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                                          01/01/1990 - 31/12/1990

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                                            01/01/1990 - 31/12/1990

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