Pierre Bruhns

Pierre Bruhns
Institut Pasteur · Department of Immunology

PhD

About

115
Publications
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7,314
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Publications

Publications (115)
Article
Full-text available
The major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is...
Article
Full-text available
The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize Omicron variant remains unclear. We...
Article
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Immunoglobulin G (IgG) is the predominant antibody class generated during infections and used for the generation of therapeutic antibodies. Antibodies are mainly characterized in or generated from animal models that support particular infections, respond to particular antigens or allow the generation of hybridomas. Due to the availability of numero...
Article
Full-text available
Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies. ASC are derived from activated B cells, which may differentiate extrafollicularly or form germinal center (GC) reactions within secondary lymphoid organs. ASC therefore consist of s...
Preprint
Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the SNARE Sec22b as a unique and critical regulator of plasma cell maintenance and function. In absence of Sec22b, plasma cells were barely detectable and serum...
Preprint
Full-text available
Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were p...
Article
Introduction La mémoire immunitaire est un mécanisme qui protège les individus contre la réinfection. Cette stratégie de défense de l’organisme, qui est à la base du succès des vaccins, comprend la production d’anticorps protecteurs dans le sang ainsi que la formation de cellules à mémoire, capables de se réactiver rapidement en cellules productric...
Article
Introduction L’émergence de variants portant des mutations dans des épitopes clés a fait craindre que l’évolution virale n’érode l’immunité acquise. Objectif Caractérisé la dynamique et la fonctionnalité de la réponse B mémoire naturelle et acquise après administration d’un vaccin à ARNm. Méthodes Nous avons analysé, au cours du temps, 33 sujets...
Article
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Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as "cryopyrin-associated periodic syndromes" (CAPS). Treatment of CAPS patients with IL-1-targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibitin...
Article
Full-text available
In addition to serum immunoglobulins, memory B cell (MBC) generation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another layer of immune protection, but the quality of MBC responses in naive and coronavirus disease 2019 (COVID-19)-recovered individuals after vaccination remains ill defined. We studied longitudinal cohort...
Article
Asthma is the most prevalent chronic respiratory disease, affecting more than 300 million people worldwide1. Although asthma is a heterogenous disease that presents with various phenotypes, around 50 % of the patients suffer from type 2 inflammation, characterized by elevated levels of IgE, type 2 cytokines such as IL‐4 and IL‐13 and eosinophilia1.
Preprint
Full-text available
The major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is...
Article
Full-text available
Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we d...
Article
Taniguchi et al . (Research Articles, 17 July 2020, p. 269) claim that the cytokine interleukin-33 induces accumulation of tumor-associated macrophages expressing the immunoglobulin E receptor FcεRI. Although these findings hold great therapeutic promise, we provide evidence that the anti-FcεRI antibody used in this study is not specific for FcεRI...
Article
Drug-induced anaphylaxis is a hyperacute reaction affecting multiple organs that can be of fatal consequence. Its incidence is increasing, consistent with a global increased sensitization to various allergens and drugs in the population. Few risk factors and mechanisms have been identified from human studies due to the rarity of anaphylactic events...
Data
Supplementary Figures 1 to 4, and Supplementary Table 1
Article
Full-text available
Antibodies with antibacterial activity need to bind to the bacterial surface with affinity, specificity, and sufficient density to induce efficient elimination. To characterize the anti-bacterial antibody repertoire, we developed an in-droplet bioassay with single-antibody resolution. The assay not only allowed us to identify whether the secreted a...
Article
Full-text available
One of the major goals of vaccination is to prepare the body to rapidly secrete specific Abs during an infection. Assessment of the vaccine quality is often difficult to perform, as simple measurements like Ab titer only partly correlate with protection. Similarly, these simple measurements are not always sensitive to changes in the preceding immun...
Article
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Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes1. We present a method for high-throughput, single-cell screening of IgG-secreting primary cells to characterize antibody binding to soluble and membrane-bound antigens. CelliGO is a droplet microfluidi...
Article
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of severe asthma and chronic spontaneous urticaria. Use of Omalizumab is associated with reported side effects, ranging from local skin inflammation at the injection site to systemic anaphylaxis. To date, the mechanisms through which Omalizumab induces adverse reactions...
Article
Full-text available
Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to...
Article
Full-text available
The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we...
Article
Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infu...
Article
Full-text available
IgG antibodies mediate the clearance of target cells via the engagement of Fc gamma receptors (FcγRs) on effector cells by eliciting antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP, respectively). Because (i) the IgG Fc domain binds to multiple FcγRs with varying affinities; (ii) even low Fc:FcγRs affinity interactions can...
Article
Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resultin...
Conference Paper
Introduction L’anaphylaxie peropératoire est une réaction d’hypersensibilité aiguë dont les principaux responsables sont les curares. Le mécanisme classique implique des IgE spécifiques et la libération d’histamine par les mastocytes et les basophiles. Cependant, des résultats de modèles animaux et d’études cliniques (étude NASA) suggèrent un mécan...
Conference Paper
Introduction L’anaphylaxie est une réaction d’hypersensibilité aiguë systémique dont le mécanisme classique fait intervenir des IgE spécifiques et la libération d’histamine par les mastocytes et les basophiles. Cependant, des données issues de modèles animaux suggèrent l’existence d’un mécanisme alternatif dépendant des IgG et de la libération de p...
Article
Full-text available
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatit...
Article
Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (Fc...
Article
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Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection of diphtheria toxin induces selective neutrophil ab...
Article
Two activating mouse IgG receptors (FcγRs) have the ability to bind monomeric IgG, the high-affinity mouse FcγRI and FcγRIV. Despite high circulating levels of IgG, reports using FcγRI−/− or FcγRIV−/− mice or FcγRIV-blocking antibodies implicate these receptors in IgG-induced disease severity or therapeutic Ab efficacy. From these studies, however,...
Article
The transcriptional repressor growth factor independence 1 (Gfi1) is important in myeloid and lymphoid differentiation. In the current study we evaluated the involvement of Gfi1 in systemic lupus erythematosus (SLE). We found that Genista mice, which carry a hypomorphic mutation in the gfi1 gene or Gfi1-deficient (Gfi1(-/-) ) mice develop signs of...
Article
Background: Anaphylaxis can proceed through distinct IgE- or IgG-dependant pathways, which have been investigated in various mouse models. We developed a novel mouse strain in which the human low-affinity IgG receptor locus, comprising both activating (hFcγRIIA, hFcγRIIIA, hFcγRIIIB) and inhibitory (hFcγRIIB) hFcγR genes, has been inserted into th...
Article
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Although most vaccines against blood stage malaria in development today use subunit preparations, live attenuated parasites confer significantly broader and more lasting protection. In recent years, Plasmodium genetically attenuated parasites (GAPs) have been generated in rodent models that cause self-resolving blood stage infections and induce str...
Article
Background: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes. Objective:...
Article
In this issue of Cancer Cell, Dahan and colleagues demonstrate that modified Fc regions of agonistic anti-human CD40 mAbs can drastically increase their efficiency in a mouse pre-clinical model expressing human CD40 and IgG receptors. This study also highlights the fine balance between increased treatment efficacy and secondary side effects.
Article
Background: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (FcγRs). Mouse IgG2a and IgG2b bind activating FcγRI, FcγRIII, and FcγRIV and inhibitory FcγRIIB; mouse IgG1 binds only FcγRIII and FcγRIIB. Although these interactions are of strikingly different affin...
Article
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Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenes...
Article
Mouse and human FcRs have been a major focus of attention not only of the scientific community, through the cloning and characterization of novel receptors, and of the medical community, through the identification of polymorphisms and linkage to disease but also of the pharmaceutical community, through the identification of FcRs as targets for ther...
Article
Introduction Le bilan étiologique classique d’un choc anaphylactique aux curares (CAC) comprend le dosage des IgE anti-ammonium quaternaire (AQ, structure commune des différents curares), réalisé grâce à un dérivé morphinique. Dans 10 % des cas, ce bilan est négatif. Des résultats expérimentaux chez la souris proposent un rôle des neutrophiles et d...
Article
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Inflammation adversely affects the health of millions of people worldwide, and there is an unmet medical need for better anti-inflammatory drugs. We evaluated the therapeutic interest of mycolactone, a polyketide-derived macrolide produced by Mycobacterium ulcerans. Bacterial production of mycolactone in human skin causes a combination of ulcerativ...
Article
Full-text available
Intravenous Igs (IVIg) therapy is widely used as an immunomodulatory strategy in inflammatory pathologies and is suggested to promote cancer regression. Because progression of tumors depends on their ability to redirect the polarization state of tumor-associated macrophages (from M1/immunogenic/proinflammatory to M2/anti-inflammatory), we have eval...
Article
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Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through the interaction between RA IgG immune complexes and IgG Fc receptors on immune cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA (hFcγRIIA) are associated with an increased risk of developing RA. Within the hFcγRIIA intracytoplasmic domain, th...
Article
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Trastuzumab is established as treatment of HER2high metastatic breast cancers but many limitations impair its efficacy. Here, we report the design of a Fab-like bispecific antibody (HER2bsFab) that displays a moderate affinity for HER2 and a unique, specific and high affinity for FcγRIII. In vitro characterization showed that ADCC was the major mec...
Article
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The biological activities of human IgG antibodies predominantly rely on a family of receptors for the Fc portion of IgG, FcγRs: FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, FcRL5, FcRn, and TRIM21. All FcγRs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG once internalized. The affinity of FcγRs for IgG is determined by...
Article
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Dendritic cells (DCs) and macrophages use various receptors to recognize foreign antigens and to receive feedback control from adaptive immune cells. Although it was long believed that all immunoglobulin Fc receptors are universally expressed by phagocytes, recent findings indicate that only monocyte-derived DCs and macrophages express high levels...