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Gilles Dietrich

Bio: Gilles Dietrich is an academic researcher from University of Toulouse. The author has contributed to research in topics: Autoantibody & Opioid receptor. The author has an hindex of 30, co-authored 71 publications receiving 2798 citations. Previous affiliations of Gilles Dietrich include Centre national de la recherche scientifique & Université catholique de Louvain.


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TL;DR: Oral treatment with Elafin-expressing food-grade bacteria protected the gut from inflammatory damage and restored intestinal homeostasis in mouse models of acute and chronic colitis, and suggested that oral delivery of LAB secreting ElafIn may be useful for treating IBD in humans.
Abstract: Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.

208 citations

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TL;DR: It is suggested that IVIg may be efficient in selected autoimmune diseases by providing a source of anti-idiotypes with a wide range of specificities brought as interconnected antibody species that may conpensate for altered connectivity of the immune network of patients with autoimmune diseases.
Abstract: This manuscript summarizes observations indicating that anti-idiotypes against human autoantibodies may be found in sera from patients recovered from autoimmune disease and in pooled normal polyspecific immunoglobulins (IVIg). The evidence that IVIg contain anti-idiotypes against autoantibodies includes: 1) inhibition by F(ab)2 from IVIg of the binding of F(ab)2 autoantibodies to their autoantigens; 2) specific retention of autoantibodies upon affinity chromatography of F(ab)2 fragments containing autoantibody activity on Sepharose-bound F(ab)2 from IVIg; 3) lack of detection of anti-allotypes and lack of significant anti-Fc activity in IVIg; 4) specific competitive displacement by polyclonal heterologous F(ab)2 anti-idiotypes of the binding of IVIg to affinity-purified F(ab)2 autoantibodies. The high number of donors contributing to IVIg endows the preparations with anti-idiotypic specificities that may not necessarily be detectable in plasma from single healthy individuals. Our observations of the presence in IVIg of anti-idiotypes against pathogenic autoantibodies and against IgG and IgM autoantibodies found in low amounts in normal sera supports the concept of a functional network regulating expression of autoimmunity in humans. We suggest that IVIg may be efficient in selected autoimmune diseases by providing a source of anti-idiotypes with a wide range of specificities brought as interconnected antibody species that may conpensate for altered connectivity of the immune network of patients with autoimmune diseases.

182 citations

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TL;DR: It is demonstrated that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals as well as natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FV III molecule.
Abstract: Spontaneous inhibitors of factor VIII (FVIII) are pathogenic IgG autoantibodies of restricted isotypic heterogeneity found in the plasma of patients presenting with bleeding episodes and low levels of FVIII. We now report the presence of a natural FVIII-neutralizing activity in 85 of 500 plasma samples (17%) from healthy donors. FVIII-inhibitory activity was present in F(ab')2 fragments of purified IgG and was dose-dependent. The titer of anti-FVIII antibodies in normal plasma ranged between 0.4 (threshold of detection) and 2.0 Bethesda units. Anti-FVIII IgG was also detected in normal plasma by using an ELISA. Anti-FVIII antibodies from healthy individuals did not exhibit restricted isotypic heterogeneity. Mean levels of FVIII activity did not differ significantly between individuals with and without detectable anti-FVIII antibodies in plasma. Natural anti-FVIII IgG inhibited FVIII activity in pools of normal plasma and in plasma of certain donors in the pool but did not inhibit FVIII activity in autologous plasma. These observations demonstrate that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals. The antibodies are natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FVIII molecule.

157 citations

Journal ArticleDOI
TL;DR: In addition to its use as substitute therapy for primary and secondary immunodeficiencies, intravenous immunoglobulin (i.v.Ig) is increasingly being used as an immunomodulating therapy in the treatment of patients with a variety of autoimmune and systemic inflammatory disorders.
Abstract: In addition to its use as substitute therapy for primary and secondary immunodeficiencies, intravenous immunoglobulin (i.v.Ig) is increasingly being used as an immunomodulating therapy in the treatment of patients with a variety of autoimmune and systemic inflammatory disorders (Schwartz 1990, Dietrich et al. 1992b, Dwyer 1992, Ronda et al. 1993). The use of i.v.Ig in these situations is supported by a few randomized clinical trials and a large number of uncontrolled and smaller studies. Of relevance to this chapter are that the reported beneficial effects of i.v.Ig include those in autoantibody-mediated autoimmune diseases (e.g., autoimmune cytopenias, anti-factor VIII autoimmune disease) as well as diseases in which autoaggressive T cells are primarily involved in the pathogenesis (e.g., autoimmune uveitis) (Imbach et al. 1981, Bussel et al. 1983, Sultan et al. 1984, McGuire et al. 1987, LeHoang et al. 1994). Where it is a feature of the disease, successful outcome of i.v.Ig therapy is associated with an improvement in the patient's systemic inflammatory condition. Modulation of B-cell and Tcell functions and of cytokine production has further been observed in animal models of autoimmune diseases following administration of human i.v.Ig or of normal homologous IgG (Forsgren et al. 1991, Rossi et al. 1991a, Saoudi et al. 1993, Hentati et al. 1994). The design of trials to establish the efficacy and appropriate therapeutic sched-

156 citations

Journal ArticleDOI
TL;DR: Results support the concept that IVIg may be beneficial in selected autoimmune diseases by modulating the function of the idiotypic network.
Abstract: Pooled normal polyspecific IgG for therapeutic use (IVIg) contain anti-idiotypes against idiotypic determinants expressed by autoantibodies from patients with a variety of autoimmune diseases. In the present study, antiidiotypes in IVIg are shown to recognize a cross-reactive idiotype on human anti-thyroglobulin (TG) autoantibodies, that was defined by heterologous antiidiotypic antibodies, termed anti-T44 antibodies. The T44 idiotype is located outside the antibody-combining site of anti-TG autoantibodies. F(ab')2 fragments from anti-T44 antibodies inhibited the binding of IVIg to affinitypurified F(ab')2 anti-TG autoantibodies. Anti-T44 antibodies bound to F(ab')2 fragments of patients' antibodies, which were retained on an affinity column of Sepharose-bound F(ab')2 fragments from IVIg, but not to F(ab')2 fragments from the effluent of the column. The T44 idiotype was expressed on antibodies that bound to IVIg from eight of nine patients with autoimmune thyroiditis, but not on IVIg-binding Igs from healthy individuals. A small amount of the T44 idiotype was also expressed on the fraction ofIVIg that bound to itselfupon affinity chromatography. The T44 idiotype was cross-reactive between antibodies from patients with autoimmune thyroiditis. Thus, IVIg contain antiidiotypic antibodies directed against an immunodominant disease-associated cross-reactive a-idiotype of human anti-TG autoantibodies. These results support the concept that IVIg may be beneficial in selected autoimmune diseases by modulating the function of the idiotypic network. (J. Clin. Invest. 1990. 85:620-625.) idiotypes - idiotypic network * autoimmune thyroiditis - autoimmunity * intravenous immunoglobulins

147 citations


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2,378 citations

Journal ArticleDOI
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

1,775 citations

Journal ArticleDOI
Marc Daëron1
TL;DR: In this paper, a review of membrane Fc receptors (FcR) of the immunoglobulin superfamily is presented, focusing on the mechanisms by which FcR trigger and regulate biological responses of cells on which they are expressed.
Abstract: ▪ Abstract This review deals with membrane Fc receptors (FcR) of the immunoglobulin superfamily. It is focused on the mechanisms by which FcR trigger and regulate biological responses of cells on which they are expressed. FcR deliver signals when they are aggregated at the cell surface. The aggregation of FcR having immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially src family tyrosine kinases and syk family tyrosine kinases that connect transduced signals to common activation pathways shared with other receptors. FcR with ITAMs elicit cell activation, endocytosis, and phagocytosis. The nature of responses depends primarily on the cell type. The aggregation of FcR without ITAM does not trigger cell activation. Most of these FcR internalize their ligands, which can be endocytosed, phagocytosed, or transcytosed. The fate of internalized receptor-ligand complexes depends on defined sequences in the intracytoplasmic domain of the receptors. The coaggregation of different FcR result...

1,331 citations

Journal ArticleDOI
TL;DR: Some of the molecules involved in the paracrine effects of MSCs are identified with a perspective that these cells intrinsically belong to a perivascular niche in vivo, and how this knowledge could be advantageously used in clinical applications is discussed.

1,254 citations