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Luisa Imberti

Bio: Luisa Imberti is an academic researcher from Canadian Real Estate Association. The author has contributed to research in topics: T cell & Medicine. The author has an hindex of 30, co-authored 141 publications receiving 5215 citations.


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Paul Bastard1, Paul Bastard2, Paul Bastard3, Lindsey B. Rosen4, Qian Zhang3, Eleftherios Michailidis3, Hans-Heinrich Hoffmann3, Yu Zhang4, Karim Dorgham1, Quentin Philippot2, Quentin Philippot1, Jérémie Rosain2, Jérémie Rosain1, Vivien Béziat3, Vivien Béziat1, Vivien Béziat2, Jeremy Manry2, Jeremy Manry1, Elana Shaw4, Liis Haljasmägi5, Pärt Peterson5, Lazaro Lorenzo2, Lazaro Lorenzo1, Lucy Bizien2, Lucy Bizien1, Sophie Trouillet-Assant6, Kerry Dobbs4, Adriana Almeida de Jesus4, Alexandre Belot6, Anne Kallaste7, Emilie Catherinot, Yacine Tandjaoui-Lambiotte2, Jérémie Le Pen3, Gaspard Kerner2, Gaspard Kerner1, Benedetta Bigio3, Yoann Seeleuthner1, Yoann Seeleuthner2, Rui Yang3, Alexandre Bolze, András N Spaan3, András N Spaan8, Ottavia M. Delmonte4, Michael S. Abers4, Alessandro Aiuti9, Giorgio Casari9, Vito Lampasona9, Lorenzo Piemonti9, Fabio Ciceri9, Kaya Bilguvar10, Richard P. Lifton3, Richard P. Lifton10, Marc Vasse, David M. Smadja1, Mélanie Migaud2, Mélanie Migaud1, Jérôme Hadjadj1, Benjamin Terrier1, Darragh Duffy11, Lluis Quintana-Murci11, Lluis Quintana-Murci12, Diederik van de Beek13, Lucie Roussel14, Donald C. Vinh14, Stuart G. Tangye15, Stuart G. Tangye16, Filomeen Haerynck17, David Dalmau18, Javier Martinez-Picado19, Javier Martinez-Picado20, Petter Brodin21, Petter Brodin22, Michel C. Nussenzweig3, Michel C. Nussenzweig23, Stéphanie Boisson-Dupuis1, Stéphanie Boisson-Dupuis2, Stéphanie Boisson-Dupuis3, Carlos Rodríguez-Gallego, Guillaume Vogt1, Trine H. Mogensen24, Trine H. Mogensen25, Andrew J. Oler4, Jingwen Gu4, Peter D. Burbelo4, Jeffrey I. Cohen4, Andrea Biondi26, Laura Rachele Bettini26, Mariella D'Angiò26, Paolo Bonfanti26, Patrick Rossignol27, Julien Mayaux1, Frédéric Rieux-Laucat1, Eystein S. Husebye28, Eystein S. Husebye29, Eystein S. Husebye30, Francesca Fusco, Matilde Valeria Ursini, Luisa Imberti31, Alessandra Sottini31, Simone Paghera31, Eugenia Quiros-Roldan32, Camillo Rossi, Riccardo Castagnoli33, Daniela Montagna33, Amelia Licari33, Gian Luigi Marseglia33, Xavier Duval, Jade Ghosn1, Hgid Lab4, Covid Clinicians5, Covid-Storm Clinicians§4, CoV-Contact Cohort§1, Amsterdam Umc Covid Biobank1, Amsterdam Umc Covid Biobank3, Amsterdam Umc Covid Biobank2, Covid Human Genetic Effort3, John S. Tsang4, Raphaela Goldbach-Mansky4, Kai Kisand5, Michail S. Lionakis4, Anne Puel3, Anne Puel2, Anne Puel1, Shen-Ying Zhang1, Shen-Ying Zhang3, Shen-Ying Zhang2, Steven M. Holland4, Guy Gorochov1, Emmanuelle Jouanguy3, Emmanuelle Jouanguy1, Emmanuelle Jouanguy2, Charles M. Rice3, Aurélie Cobat3, Aurélie Cobat1, Aurélie Cobat2, Luigi D. Notarangelo4, Laurent Abel1, Laurent Abel3, Laurent Abel2, Helen C. Su4, Jean-Laurent Casanova 
23 Oct 2020-Science
TL;DR: A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested.
Abstract: Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

1,913 citations

Journal ArticleDOI
Qian Zhang1, Paul Bastard2, Paul Bastard3, Zhiyong Liu1  +169 moreInstitutions (34)
23 Oct 2020-Science
TL;DR: The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001.
Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

1,659 citations

Journal ArticleDOI
29 May 1998-Cell
TL;DR: It is reported here that patients with Omenn syndrome, a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia, and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes that result in partial activity of the two proteins.

422 citations

Journal ArticleDOI
TL;DR: In this paper, the authors found that auto-antibodies neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections.
Abstract: Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

269 citations

Journal ArticleDOI
TL;DR: Levels of sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
Abstract: Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

248 citations


Cited by
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08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: A previously unrecognized pathway for the activation of tumor antigen–specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs) is described.
Abstract: Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.

2,666 citations

Journal ArticleDOI
TL;DR: It is postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies and its subversion by pathogens.
Abstract: Depending on the initiating stimulus, cancer cell death can be immunogenic or nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition of the cell surface as well as the release of soluble mediators, occurring in a defined temporal sequence. Such signals operate on a series of receptors expressed by dendritic cells to stimulate the presentation of tumor antigens to T cells. We postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies. Hence, suboptimal regimens (failing to induce ICD), selective alterations in cancer cells (preventing the emission of immunogenic signals during ICD), or defects in immune effectors (abolishing the perception of ICD by the immune system) can all contribute to therapeutic failure. We surmise that ICD and its subversion by pathogens also play major roles in antiviral immune responses.

2,323 citations

Journal ArticleDOI
05 Feb 2021-Science
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
Abstract: Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

1,980 citations