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1,079 results on '"Sallusto, Federica"'

1. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells

Author

Thakore, Pratiksha I., Schnell, Alexandra, Huang, Linglin, Zhao, Maryann, Hou, Yu, Christian, Elena, Zaghouani, Sarah, Wang, Chao, Singh, Vasundhara, Singaraju, Anvita, Krishnan, Rajesh Kumar, Kozoriz, Deneen, Ma, Sai, Sankar, Venkat, Notarbartolo, Samuele, Buenrostro, Jason D., Sallusto, Federica, Patsopoulos, Nikolaos A., Rozenblatt-Rosen, Orit, Kuchroo, Vijay K., and Regev, Aviv

Published
2024
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6. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

Author

Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O’Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, Investigators, The ISARIC4C, Consortium, the COVID-19 Genomics UK, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, and Snell, Gyorgy

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Immunology, Pneumonia, Prevention, Infectious Diseases, Vaccine Related, Immunization, Pneumonia & Influenza, Biodefense, Biotechnology, Emerging Infectious Diseases, Lung, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Angiotensin-Converting Enzyme 2, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Genetic Fitness, Humans, Immune Evasion, Mutation, Phylogeny, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Virulence, ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium, N439K, Spike, monoclonal antibody escape, mutation, protein structure, receptor binding motif, variant, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Published
2021

7. Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria

Author

Bohlen, Jonathan, Zhou, Qinhua, Philippot, Quentin, Ogishi, Masato, Rinchai, Darawan, Nieminen, Tea, Seyedpour, Simin, Parvaneh, Nima, Rezaei, Nima, Yazdanpanah, Niloufar, Momenilandi, Mana, Conil, Clément, Neehus, Anna-Lena, Schmidt, Carltin, Arango-Franco, Carlos A., Voyer, Tom Le, Khan, Taushif, Yang, Rui, Puchan, Julia, Erazo, Lucia, Roiuk, Mykola, Vatovec, Taja, Janda, Zarah, Bagarić, Ivan, Materna, Marie, Gervais, Adrian, Li, Hailun, Rosain, Jérémie, Peel, Jessica N, Seeleuthner, Yoann, Han, Ji Eun, L’Honneur, Anne-Sophie, Moncada-Vélez, Marcela, Martin-Fernandez, Marta, Horesh, Michael E., Kochetkov, Tatiana, Schmidt, Monika, AlShehri, Mohammed A., Salo, Eeva, Saxen, Harri, ElGhazali, Gehad, Yatim, Ahmad, Soudée, Camille, Sallusto, Federica, Ensser, Armin, Marr, Nico, Zhang, Peng, Bogunovic, Dusan, Cobat, Aurélie, Shahrooei, Mohammad, Béziat, Vivien, Abel, Laurent, Wang, Xiaochuan, Boisson-Dupuis, Stéphanie, Teleman, Aurelio A., Bustamante, Jacinta, Zhang, Qian, and Casanova, Jean-Laurent

Published
2023
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9. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

Author

Piccoli, Luca, Park, Young-Jun, Tortorici, M Alejandra, Czudnochowski, Nadine, Walls, Alexandra C, Beltramello, Martina, Silacci-Fregni, Chiara, Pinto, Dora, Rosen, Laura E, Bowen, John E, Acton, Oliver J, Jaconi, Stefano, Guarino, Barbara, Minola, Andrea, Zatta, Fabrizia, Sprugasci, Nicole, Bassi, Jessica, Peter, Alessia, De Marco, Anna, Nix, Jay C, Mele, Federico, Jovic, Sandra, Rodriguez, Blanca Fernandez, Gupta, Sneha V, Jin, Feng, Piumatti, Giovanni, Lo Presti, Giorgia, Pellanda, Alessandra Franzetti, Biggiogero, Maira, Tarkowski, Maciej, Pizzuto, Matteo S, Cameroni, Elisabetta, Havenar-Daughton, Colin, Smithey, Megan, Hong, David, Lepori, Valentino, Albanese, Emiliano, Ceschi, Alessandro, Bernasconi, Enos, Elzi, Luigia, Ferrari, Paolo, Garzoni, Christian, Riva, Agostino, Snell, Gyorgy, Sallusto, Federica, Fink, Katja, Virgin, Herbert W, Lanzavecchia, Antonio, Corti, Davide, and Veesler, David

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Clinical Research, Lung, Pneumonia & Influenza, Biodefense, Immunization, Prevention, Infectious Diseases, Pneumonia, Vaccine Related, Emerging Infectious Diseases, Infection, Good Health and Well Being, Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antigen-Antibody Reactions, Betacoronavirus, Binding Sites, COVID-19, Coronavirus Infections, Epitope Mapping, Epitopes, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Kinetics, Molecular Dynamics Simulation, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Binding, Protein Domains, Protein Structure, Quaternary, SARS-CoV-2, Spike Glycoprotein, Coronavirus, coronaviruses, effector functions, immunity, neutralizing antibodies, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Published
2020

11. Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

Author

Marzi, Roberta, Bassi, Jessica, Silacci-Fregni, Chiara, Bartha, Istvan, Muoio, Francesco, Culap, Katja, Sprugasci, Nicole, Lombardo, Gloria, Saliba, Christian, Cameroni, Elisabetta, Cassotta, Antonino, Low, Jun Siong, Walls, Alexandra C., McCallum, Matthew, Tortorici, M. Alejandra, Bowen, John E., Dellota, Exequiel A., Jr., Dillen, Josh R., Czudnochowski, Nadine, Pertusini, Laura, Terrot, Tatiana, Lepori, Valentino, Tarkowski, Maciej, Riva, Agostino, Biggiogero, Maira, Franzetti-Pellanda, Alessandra, Garzoni, Christian, Ferrari, Paolo, Ceschi, Alessandro, Giannini, Olivier, Havenar-Daughton, Colin, Telenti, Amalio, Arvin, Ann, Virgin, Herbert W., Sallusto, Federica, Veesler, David, Lanzavecchia, Antonio, Corti, Davide, and Piccoli, Luca

Published
2023
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13. Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes.

Author

Paparoditis, Philipp C. G., Fruehwirth, Alexander, Bevc, Kajetana, Low, Jun Siong, Jerak, Josipa, Terzaghi, Laura, Foglierini, Mathilde, Fernandez, Blanca, Jarrossay, David, Corti, Davide, Sallusto, Federica, Lanzavecchia, Antonio, and Cassotta, Antonino

Subjects
TRANSMISSIBLE tumors, ANTIBODY formation, IMMUNE response, COMMUNICABLE diseases, MONOCLONAL antibodies
Abstract

Efficient identification of human monoclonal antibodies targeting specific antigenic sites is pivotal for advancing vaccines and immunotherapies against infectious diseases and cancer. Existing screening techniques, however, limit our ability to discover monoclonal antibodies with desired specificity. In this study, we introduce a novel method, blocking of binding (BoB) enzyme‐linked immunoassay (ELISA), enabling the detection of high‐avidity human antibodies directed to defined epitopes. Leveraging BoB‐ELISA, we analyzed the antibody response to known epitopes of influenza A hemagglutinin (HA) in the serum of vaccinated donors. Our findings revealed that serum antibodies targeting head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent. Extending our analysis across multiple HA strains, we examined the cross‐reactive antibody response targeting the stem epitope. Importantly, employing BoB‐ELISA we identified donors harboring potent heterosubtypic antibodies targeting the HA stem. B‐cell clonal analysis of these donors revealed three novel, genealogically independent monoclonal antibodies with broad cross‐reactivity to multiple HAs. In summary, we demonstrated that BoB‐ELISA is a sensitive technique for measuring B‐cell epitope immunogenicity, enabling the identification of novel monoclonal antibodies with implications for enhanced vaccine development and immunotherapies. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Metabolic modulation of tumours with engineered bacteria for immunotherapy

Author

Canale, Fernando P., Basso, Camilla, Antonini, Gaia, Perotti, Michela, Li, Ning, Sokolovska, Anna, Neumann, Julia, James, Michael J., Geiger, Stefania, Jin, Wenjie, Theurillat, Jean-Philippe, West, Kip A., Leventhal, Daniel S., Lora, Jose M., Sallusto, Federica, and Geiger, Roger

Subjects
Metabolism -- Health aspects, Tumors -- Care and treatment, Bacteria -- Usage -- Health aspects, Immunotherapy -- Methods, Genetically modified organisms -- Usage -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The availability of l-arginine in tumours is a key determinant of an efficient anti-tumour T cell response.sup.1-4. Consequently, increases of typically low l-arginine concentrations within the tumour may greatly potentiate the anti-tumour responses of immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1)-blocking antibodies.sup.5. However, currently no means are available to locally increase intratumoural l-arginine levels. Here we used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumours and continuously converts ammonia, a metabolic waste product that accumulates in tumours.sup.6, to l-arginine. Colonization of tumours with these bacteria increased intratumoural l-arginine concentrations, increased the number of tumour-infiltrating T cells and had marked synergistic effects with PD-L1 blocking antibodies in the clearance of tumours. The anti-tumour effect of these bacteria was mediated by l-arginine and was dependent on T cells. These results show that engineered microbial therapies enable metabolic modulation of the tumour microenvironment leading to enhanced efficacy of immunotherapies. Injection of engineered bacteria that convert ammonia to l-arginine into tumours enhance the anti-tumour response in a mouse model and synergize with anti-PD-L1 treatment to clear tumours., Author(s): Fernando P. Canale [sup.1] , Camilla Basso [sup.1] [sup.5] , Gaia Antonini [sup.1] , Michela Perotti [sup.1] [sup.2] , Ning Li [sup.3] , Anna Sokolovska [sup.3] , Julia Neumann [...]

Published
2021
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15. Activin-A limits Th17 pathogenicity and autoimmune neuroinflammation via CD39 and CD73 ectonucleotidases and Hif1-α–dependent pathways

Author

Morianos, Ioannis, Trochoutsou, Aikaterini I., Papadopoulou, Gina, Semitekolou, Maria, Banos, Aggelos, Konstantopoulos, Dimitris, Manousopoulou, Antigoni, Kapasa, Maria, Wei, Ping, Lomenick, Brett, Belaidi, Elise, Kalamatas, Themis, Karageorgiou, Klinta, Doskas, Triantafyllos, Sallusto, Federica, Pan, Fan, Garbis, Spiros D., Quintana, Francisco J., and Xanthou, Georgina

Published
2020

17. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author

Ingelfinger, Florian, Krishnarajah, Sinduya, Kramer, Michael, Utz, Sebastian G., Galli, Edoardo, Lutz, Mirjam, Zwicky, Pascale, Akarca, Ayse U., Jurado, Nicole Puertas, Ulutekin, Can, Bamert, David, Widmer, Corinne C., Piccoli, Luca, Sallusto, Federica, Núñez, Nicolás G., Marafioti, Teresa, Schneiter, Didier, Opitz, Isabelle, Lanzavecchia, Antonio, Jung, Hans H., De Feo, Donatella, Mundt, Sarah, Schreiner, Bettina, and Becher, Burkhard

Published
2021
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22. Dynamics in protein translation sustaining T cell preparedness

Author

Wolf, Tobias, Jin, Wenjie, Zoppi, Giada, Vogel, Ian A., Akhmedov, Murodzhon, Bleck, Christopher K. E., Beltraminelli, Tim, Rieckmann, Jan C., Ramirez, Neftali J., Benevento, Marco, Notarbartolo, Samuele, Bumann, Dirk, Meissner, Felix, Grimbacher, Bodo, Mann, Matthias, Lanzavecchia, Antonio, Sallusto, Federica, Kwee, Ivo, and Geiger, Roger

Published
2020
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25. A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Author

Cassotta, Antonino, Mikol, Vincent, Bertrand, Thomas, Pouzieux, Stéphanie, Le Parc, Josiane, Ferrari, Paul, Dumas, Jacques, Auer, Michael, Deisenhammer, Florian, Gastaldi, Matteo, Franciotta, Diego, Silacci-Fregni, Chiara, Fernandez Rodriguez, Blanca, Giacchetto-Sasselli, Isabella, Foglierini, Mathilde, Jarrossay, David, Geiger, Roger, Sallusto, Federica, Lanzavecchia, Antonio, and Piccoli, Luca

Published
2019
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30. Correction to: Single‑cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author

Ingelfinger, Florian, Krishnarajah, Sinduya, Kramer, Michael, Utz, Sebastian G., Galli, Edoardo, Lutz, Mirjam, Zwicky, Pascale, Akarca, Ayse U., Jurado, Nicole Puertas, Ulutekin, Can, Bamert, David, Widmer, Corinne C., Piccoli, Luca, Sallusto, Federica, Núñez, Nicolás G., Marafioti, Teresa, Schneiter, Didier, Opitz, Isabelle, Lanzavecchia, Antonio, Jung, Hans H., De Feo, Donatella, Mundt, Sarah, Schreiner, Bettina, and Becher, Burkhard

Published
2021
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31. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein

Author

Tan, Joshua, Sack, Brandon K, Oyen, David, Zenklusen, Isabelle, Piccoli, Luca, Barbieri, Sonia, Foglierini, Mathilde, Fregni, Chiara Silacci, Marcandalli, Jessica, Jongo, Said, Abdulla, Salim, Perez, Laurent, Corradin, Giampietro, Varani, Luca, Sallusto, Federica, Sim, Betty Kim Lee, Hoffman, Stephen L, Kappe, Stefan H I, Daubenberger, Claudia, Wilson, Ian A, and Lanzavecchia, Antonio

Subjects
Monoclonal antibodies -- Health aspects, Molecular targeted therapy -- Innovations, Malaria -- Genetic aspects -- Development and progression -- Care and treatment, Immunoglobulins -- Health aspects, Biological sciences, Health
Abstract

Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies., Author(s): Joshua Tan [1, 2]; Brandon K Sack [3]; David Oyen [4]; Isabelle Zenklusen [5, 6]; Luca Piccoli [1]; Sonia Barbieri [1]; Mathilde Foglierini [1, 7]; Chiara Silacci Fregni [1]; [...]

Published
2018
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32. Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency

Author

Kong, Xiao-Fei, Martinez-Barricarte, Ruben, Kennedy, James, Mele, Federico, Lazarov, Tomi, Deenick, Elissa K., Ma, Cindy S., Breton, Gaëlle, Lucero, Kimberly B., Langlais, David, Bousfiha, Aziz, Aytekin, Caner, Markle, Janet, Trouillet, Céline, Jabot-Hanin, Fabienne, Arlehamn, Cecilia S. Lindestam, Rao, Geetha, Picard, Capucine, Lasseau, Théo, Latorre, Daniela, Hambleton, Sophie, Deswarte, Caroline, Itan, Yuval, Abarca, Katia, Moraes-Vasconcelos, Dewton, Ailal, Fatima, Ikinciogullari, Aydan, Dogu, Figen, Benhsaien, Ibtihal, Sette, Alessandro, Abel, Laurent, Boisson-Dupuis, Stéphanie, Schröder, Bernd, Nussenzweig, Michel C., Liu, Kang, Geissmann, Frédéric, Tangye, Stuart G., Gros, Philippe, Sallusto, Federica, Bustamante, Jacinta, and Casanova, Jean-Laurent

Published
2018
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33. Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults

Author

Marcinkevics, Ricards, primary, Silva, Pamuditha N., additional, Hankele, Anna-Katharina, additional, Dörnte, Charlyn, additional, Kadelka, Sarah, additional, Csik, Katharina, additional, Godbersen, Svenja, additional, Goga, Algera, additional, Hasenöhrl, Lynn, additional, Hirschi, Pascale, additional, Kabakci, Hasan, additional, LaPierre, Mary P., additional, Mayrhofer, Johanna, additional, Title, Alexandra C., additional, Shu, Xuan, additional, Baiioud, Nouell, additional, Bernal, Sandra, additional, Dassisti, Laura, additional, Saenz-de-Juano, Mara D., additional, Schmidhauser, Meret, additional, Silvestrelli, Giulia, additional, Ulbrich, Simon Z., additional, Ulbrich, Thea J., additional, Wyss, Tamara, additional, Stekhoven, Daniel J., additional, Al-Quaddoomi, Faisal S., additional, Yu, Shuqing, additional, Binder, Mascha, additional, Schultheiβ, Christoph, additional, Zindel, Claudia, additional, Kolling, Christoph, additional, Goldhahn, Jörg, additional, Seighalani, Bahram Kasmapour, additional, Zjablovskaja, Polina, additional, Hardung, Frank, additional, Schuster, Marc, additional, Richter, Anne, additional, Huang, Yi-Ju, additional, Lauer, Gereon, additional, Baurmann, Herrad, additional, Low, Jun Siong, additional, Vaqueirinho, Daniela, additional, Jovic, Sandra, additional, Piccoli, Luca, additional, Ciesek, Sandra, additional, Vogt, Julia E., additional, Sallusto, Federica, additional, Stoffel, Markus, additional, and Ulbrich, Susanne E., additional

Published
2023
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35. Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Author

Ingelfinger, Florian, Kramer, Michael, Lutz, Mirjam, Widmer, Corinne C, Piccoli, Luca; https://orcid.org/0000-0002-1085-6502, Kreutmair, Stefanie; https://orcid.org/0000-0001-8466-6675, Wertheimer, Tobias, Woodhall, Mark, Waters, Patrick, Sallusto, Federica, Lanzavecchia, Antonio, Mundt, Sarah, Becher, Burkhard; https://orcid.org/0000-0002-1541-7867, Schreiner, Bettina, Ingelfinger, Florian, Kramer, Michael, Lutz, Mirjam, Widmer, Corinne C, Piccoli, Luca; https://orcid.org/0000-0002-1085-6502, Kreutmair, Stefanie; https://orcid.org/0000-0001-8466-6675, Wertheimer, Tobias, Woodhall, Mark, Waters, Patrick, Sallusto, Federica, Lanzavecchia, Antonio, Mundt, Sarah, Becher, Burkhard; https://orcid.org/0000-0002-1541-7867, and Schreiner, Bettina

Abstract

BACKGROUND AND OBJECTIVES Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates. METHODS We identified patients with acetylcholine receptor antibody-positive (AChR$^{+}$) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding. RESULTS A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR$^{+}$ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens. DISCUSSION Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR$^{+}$ MG. CLASSIFICATION OF EVIDENCE This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG.

Published
2023

38. Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

Author

Stettler, Karin, Beltramello, Martina, Espinosa, Diego A., Graham, Victoria, Cassotta, Antonino, Bianchi, Siro, Vanzetta, Fabrizia, Minola, Andrea, Jaconi, Stefano, Mele, Federico, Foglierini, Mathilde, Pedotti, Mattia, Simonelli, Luca, Dowall, Stuart, Atkinson, Barry, Percivalle, Elena, Simmons, Cameron P., Varani, Luca, Blum, Johannes, Baldanti, Fausto, Cameroni, Elisabetta, Hewson, Roger, Harris, Eva, Lanzavecchia, Antonio, Sallusto, Federica, and Corti, Davide

Published
2016

39. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody

Author

Corti, Davide, Misasi, John, Mulangu, Sabue, Stanley, Daphne A., Kanekiyo, Masaru, Wollen, Suzanne, Ploquin, Aurélie, Doria-Rose, Nicole A., Staupe, Ryan P., Bailey, Michael, Shi, Wei, Choe, Misook, Marcus, Hadar, Thompson, Emily A., Cagigi, Alberto, Silacci, Chiara, Fernandez-Rodriguez, Blanca, Perez, Laurent, Sallusto, Federica, Vanzetta, Fabrizia, Agatic, Gloria, Cameroni, Elisabetta, Kisalu, Neville, Gordon, Ingelise, Ledgerwood, Julie E., Mascola, John R., Graham, Barney S., Muyembe-Tamfun, Jean-Jacques, Trefry, John C., Lanzavecchia, Antonio, and Sullivan, Nancy J.

Published
2016

41. Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8+ T cell formation.

Author

Franco, Fabien, Bevilacqua, Alessio, Wu, Ruey-Mei, Kao, Kung-Chi, Lin, Chun-Pu, Rousseau, Lorène, Peng, Fu-Ti, Chuang, Yu-Ming, Peng, Jhan-Jie, Park, Jaeoh, Xu, Yingxi, Cassotta, Antonino, Yu, Yi-Ru, Speiser, Daniel E., Sallusto, Federica, and Ho, Ping-Chih

Abstract

Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8+ T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8+ memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8+ T cell formation. We further uncovered that regulators of mitophagy, including Parkin and NIX, were up-regulated in response to interleukin-15 (IL-15) for supporting memory T cell formation. Mechanistically, Parkin suppressed VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells counteracted ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. Together, our results indicate that the mitophagy machinery orchestrates survival and metabolic dynamics required for memory T cell formation, as well as highlight a deficit in T cell–mediated antiviral responses in Parkinson's disease patients. Editor's summary: During an immune response, T cells rely on mitochondria to support their evolving metabolic demands. Maintenance of mitochondrial health requires removal of damaged mitochondria via mitophagy, which can occur through PINK1/Parkin- or BNIP3L/NIX-mediated pathways. Using peripheral blood from patients with Parkinson's disease and LCMV-infected mice, Franco et al. examined the function of mitochondrial quality control in memory T cell responses. Patients with Parkinson's disease, which is associated with impairments in mitophagy, had fewer CD8+ memory T cells and impaired SARS-CoV-2–specific responses after vaccination. In LCMV-infected mice, Parkin suppressed VDAC1-dependent apoptosis of memory T cells, whereas NIX restrained ferroptosis by preventing metabolic dysfunction. These results demonstrate that key pathways of mitophagy support memory T cell responses by limiting distinct forms of cell death. —Claire Olingy [ABSTRACT FROM AUTHOR]

Published
2023
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42. Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Author

Ingelfinger, Florian, primary, Kramer, Michael, additional, Lutz, Mirjam, additional, Widmer, Corinne C., additional, Piccoli, Luca, additional, Kreutmair, Stefanie, additional, Wertheimer, Tobias, additional, Woodhall, Mark, additional, Waters, Patrick, additional, Sallusto, Federica, additional, Lanzavecchia, Antonio, additional, Mundt, Sarah, additional, Becher, Burkhard, additional, and Schreiner, Bettina, additional

Published
2023
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44. SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines

Author

Bowen, John E., primary, Park, Young-Jun, additional, Stewart, Cameron, additional, Brown, Jack T., additional, Sharkey, William K., additional, Walls, Alexandra C., additional, Joshi, Anshu, additional, Sprouse, Kaitlin R., additional, McCallum, Matthew, additional, Tortorici, M. Alejandra, additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Mazzitelli, Ignacio G., additional, Nguyen, Annalee W., additional, Silva, Rui P., additional, Huang, Yimin, additional, Low, Jun Siong, additional, Jerak, Josipa, additional, Tiles, Sasha W., additional, Ahmed, Kumail, additional, Shariq, Asefa, additional, Dan, Jennifer M., additional, Zhang, Zeli, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Snell, Gyorgy, additional, Posavad, Christine M., additional, Iqbal, Najeeha Talat, additional, Geffner, Jorge, additional, Bandera, Alessandra, additional, Gori, Andrea, additional, Sallusto, Federica, additional, Maynard, Jennifer A., additional, Crotty, Shane, additional, Van Voorhis, Wesley C., additional, Simmerling, Carlos, additional, Grifantini, Renata, additional, Chu, Helen Y., additional, Corti, Davide, additional, and Veesler, David, additional

Published
2022
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46. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

Author

Okada, Satoshi, Markle, Janet G., Deenick, Elissa K., Mele, Federico, Averbuch, Dina, Lagos, Macarena, Alzahrani, Mohammed, Al-Muhsen, Saleh, Halwani, Rabih, Ma, Cindy S., Wong, Natalie, Soudais, Claire, Henderson, Lauren A., Marzouqa, Hiyam, Shamma, Jamal, Gonzalez, Marcela, Martinez-Barricarte, Rubén, Okada, Chizuru, Avery, Danielle T., Latorre, Daniela, Deswarte, Caroline, Jabot-Hanin, Fabienne, Torrado, Egidio, Fountain, Jeffrey, Belkadi, Aziz, Itan, Yuval, Boisson, Bertrand, Migaud, Mélanie, Arlehamn, Cecilia S. Lindestam, Sette, Alessandro, Breton, Sylvain, McCluskey, James, Rossjohn, Jamie, de Villartay, Jean-Pierre, Moshous, Despina, Hambleton, Sophie, Latour, Sylvain, Arkwright, Peter D., Picard, Capucine, Lantz, Olivier, Engelhard, Dan, Kobayashi, Masao, Abel, Laurent, Cooper, Andrea M., Notarangelo, Luigi D., Boisson-Dupuis, Stéphanie, Puel, Anne, Sallusto, Federica, Bustamante, Jacinta, Tangye, Stuart G., and Casanova, Jean-Laurent

Published
2015

50. Longitudinal Postvaccine SARS-CoV-2 Immunoglobulin G Titers, Memory B-Cell Responses, and Risk of COVID-19 in Multiple Sclerosis Over 1 Year

Author

Disanto, Giulio, primary, Galante, Alice, additional, Cantu', Marco, additional, Sacco, Rosaria, additional, Mele, Federico, additional, Eisler, Jennifer Jessica, additional, Keller, Franco, additional, Bernasconi, Enos, additional, Sallusto, Federica, additional, Zecca, Chiara, additional, and Gobbi, Claudio, additional

Published
2022
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