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1. Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation

Author

Botti L, Cancila, Claudio Tripodo, Mario P. Colombo, Vaenti C, Maurilio Ponzoni, Comoli P, Elena Jachetti, Antonio Curti, S. Sangaletti, Barbara Bassani, Claudia Chiodoni, Perrone M, and Portararo P

Subjects
Antigen, Chemistry, Cytoplasm, Mutant, Myeloproliferation, Cytotoxic T cell, Neutrophil extracellular traps, CD8, Epitope, Cell biology
Abstract

Neutrophil extracellular traps (NET) are web-like chromatin structures composed by dsDNA and histones, decorated with anti-microbial proteins. Their interaction with dendritic cells (DC) allows DC activation and maturation toward presentation of NET-associated antigens. Differently from other types of cell death that imply protein denaturation, NETosis preserves the proteins localized onto the DNA threads for proper enzymatic activity and conformational status, including immunogenic epitopes. Besides neutrophils, leukemic cells can release extracellular traps displaying leukemia-associated antigens, prototypically mutant nucleophosmin (NPMc+) that upon mutation translocates from nucleolus to the cytoplasm localizing onto NET threads. We tested NPMc+ immunogenicity through a NET/DC vaccine to treat NPMc-driven myeloproliferation in transgenic and transplantable models. Vaccination with DC loaded with NPMc+ NET (NPMc+ NET/DC) reduced myeloproliferation in transgenic mice, favoring the development of antibodies to mutant NPMc and and the induction of a CD8+ T cell response. The efficacy of this vaccine was also tested in mixed NPMc/WT bone marrow chimeras in a competitive bone marrow transplantation setting, where the NPMc+ NET/DC vaccination impaired the expansion of NPMc+ in favor of WT myeloid compartment. NPMc+ NET/DC vaccination also achieved control of an aggressive leukemia transduced with mutant NPMc, effectively inducing an anti-leukemia CD8 T cell memory response.eTOC SummaryNPMc is an AML-triggering mutation inducing translocation of NPM into the cytoplasm, allowing its association to NET threads. On NET, NPMc becomes immunogenic acting as an alarmin and exposing immunogenic peptides. We demonstrate that NET can be exploited as anti-tumor weapons in DC-based vaccination strategies.

Published
2021
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2. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author

Bastard, P. Gervais, A. Voyer, T.L. Rosain, J. Philippot, Q. Manry, J. Michailidis, E. Hoffmann, H.-H. Eto, S. Garcia-Prat, M. Bizien, L. Parra-Martínez, A. Yang, R. Haljasmägi, L. Migaud, M. Särekannu, K. Maslovskaja, J. De Prost, N. Tandjaoui-Lambiotte, Y. Luyt, C.-E. Amador-Borrero, B. Gaudet, A. Poissy, J. Morel, P. Richard, P. Cognasse, F. Troya, J. Trouillet-Assant, S. Belot, A. Saker, K. Garçon, P. Rivière, J.G. Lagier, J.-C. Gentile, S. Rosen, L.B. Shaw, E. Morio, T. Tanaka, J. Dalmau, D. Tharaux, P.-L. Sene, D. Stepanian, A. Megarbane, B. Triantafyllia, V. Fekkar, A. Heath, J.R. Franco, J.L. Anaya, J.-M. Solé-Violán, J. Imberti, L. Biondi, A. Bonfanti, P. Castagnoli, R. Delmonte, O.M. Zhang, Y. Snow, A.L. Holland, S.M. Biggs, C.M. Moncada-Vélez, M. Arias, A.A. Lorenzo, L. Boucherit, S. Coulibaly, B. Anglicheau, D. Planas, A.M. Haerynck, F. Duvlis, S. Nussbaum, R.L. Ozcelik, T. Keles, S. Bousfiha, A.A. El Bakkouri, J. Ramirez-Santana, C. Paul, S. Pan-Hammarström, Q. Hammarström, L. Dupont, A. Kurolap, A. Metz, C.N. Aiuti, A. Casari, G. Lampasona, V. Ciceri, F. Barreiros, L.A. Dominguez-Garrido, E. Vidigal, M. Zatz, M. Van De Beek, D. Sahanic, S. Tancevski, I. Stepanovskyy, Y. Boyarchuk, O. Nukui, Y. Tsumura, M. Vidaur, L. Tangye, S.G. Burrel, S. Duffy, D. Quintana-Murci, L. Klocperk, A. Kann, N.Y. Shcherbina, A. Lau, Y.-L. Leung, D. Coulongeat, M. Marlet, J. Koning, R. Reyes, L.F. Chauvineau-Grenier, A. Venet, F. Monneret, G. Nussenzweig, M.C. Arrestier, R. Boudhabhay, I. Baris-Feldman, H. Hagin, D. Wauters, J. Meyts, I. Dyer, A.H. Kennelly, S.P. Bourke, N.M. Halwani, R. Sharif-Askari, N.S. Dorgham, K. Sallette, J. Sedkaoui, S.M. AlKhater, S. Rigo-Bonnin, R. Morandeira, F. Roussel, L. Vinh, D.C. Ostrowski, S.R. Condino-Neto, A. Prando, C. Bondarenko, A. Spaan, A.N. Gilardin, L. Fellay, J. Lyonnet, S. Bilguvar, K. Lifton, R.P. Mane, S. Anderson, M.S. Boisson, B. Béziat, V. Zhang, S.-Y. Andreakos, E. Hermine, O. Pujol, A. Peterson, P. Mogensen, T.H. Rowen, L. Mond, J. Debette, S. De Lamballerie, X. Duval, X. Mentré, F. Zins, M. Soler-Palacin, P. Colobran, R. Gorochov, G. Solanich, X. Susen, S. Martinez-Picado, J. Raoult, D. Vasse, M. Gregersen, P.K. Piemonti, L. Rodríguez-Gallego, C. Notarangelo, L.D. Su, H.C. Kisand, K. Okada, S. Puel, A. Jouanguy, E. Rice, C.M. Tiberghien, P. Zhang, Q. Cobat, A. Abel, L. Casanova, J.-L. Alavoine, L. Behillil, S. Burdet, C. Charpentier, C. Dechanet, A. Descamps, D. Ecobichon, J.-L. Enouf, V. Frezouls, W. Houhou, N. Kafif, O. Lehacaut, J. Letrou, S. Lina, B. Lucet, J.-C. Manchon, P. Nouroudine, M. Piquard, V. Quintin, C. Thy, M. Tubiana, S. Van Der Werf, S. Vignali, V. Visseaux, B. Yazdanpanah, Y. Chahine, A. Waucquier, N. Migaud, M.-C. Deplanque, D. Djossou, F. Mergeay-Fabre, M. Lucarelli, A. Demar, M. Bruneau, L. Gerardin, P. Maillot, A. Payet, C. Laviolle, B. Laine, F. Paris, C. Desille-Dugast, M. Fouchard, J. Malvy, D. Nguyen, D. Pistone, T. Perreau, P. Gissot, V. Le Goas, C. Montagne, S. Richard, L. Chirouze, C. Bouiller, K. Desmarets, M. Meunier, A. Lefevre, B. Jeulin, H. Legrand, K. Lomazzi, S. Tardy, B. Gagneux-Brunon, A. Bertholon, F. Botelho-Nevers, E. Christelle, K. Nicolas, L. Roufai, L. Amat, K. Couffin-Cadiergues, S. Esperou, H. Hendou, S. Townsend, L. Cheallaigh, C.N. Bergin, C. Martin-Loeches, I. Dunne, J. Conlon, N. O'Farrelly, C. Abad, J. Accordino, G. Achille, C. Aguilera-Albesa, S. Aguilo-Cucurull, A. Ozkan, E.A. Darazam, I.A. Albisures, J.A.R. Aldave, J.C. Ramos, M.A. Khan, T.A. Aliberti, A. Nadji, S.A. Alkan, G. AlKhater, S.A. Allardet-Servent, J. Allende, L.M. Alonso-Arias, R. Alshahrani, M.S. Alsina, L. Alyanakian, M.-A. Borrero, B.A. Amoura, Z. Antoli, A. Aubart, M. Auguet, T. Avramenko, I. Aytekin, G. Azot, A. Bahram, S. Bajolle, F. Baldanti, F. Baldolli, A. Ballester, M. Feldman, H.B. Barrou, B. Barzaghi, F. Basso, S. Bayhan, G.I. Bezrodnik, L. Bilbao, A. Blanchard-Rohner, G. Blanco, I. Blandinieres, A. Blazquez-Gamero, D. Bleibtreu, A. Bloomfield, M. Bolivar-Prados, M. Borghesi, A. Borie, R. Botdhlo-Nevers, E. Bousquet, A. Boutolleau, D. Bouvattier, C. Bravais, J. Briones, M.L. Brunner, M.-E. Bruno, R. Bueno, M.R.P. Bukhari, H. Bustamante, J. Agra, J.J.C. Capra, R. Carapito, R. Carrabba, M. Casasnovas, C. Caseris, M. Cassaniti, I. Castelle, M. Castelli, F. De Vera, M.C. Castro, M.V. Catherinot, E. Celik, J.B. Ceschi, A. Chalumeau, M. Charbit, B. Cheng, M.P. Clave, P. Clotet, B. Codina, A. Cohen, Y. Comarmond, C. Combes, A. Comoli, P. Corsico, A.G. Coşkuner, T. Cvetkovski, A. Cyrus, C. Danion, F. Darley, D.R. Das, V. Dauby, N. Dauger, S. De Munter, P. De Pontual, L. Dehban, A. Delplancq, G. Demoule, A. Desguerre, I. Di Sabatino, A. Diehl, J.-L. Dobbelaere, S. Dubost, C. Ekwall, O. Bozdemir, Ş.E. Elnagdy, M.H. Emiroglu, M. Endo, A. Erdeniz, E.H. Aytekin, S.E. Lasa, M.P.E. Euvrard, R. Fabio, G. Faivre, L. Falck, A. Fartoukh, M. Faure, M. Arquero, M.F. Ferrer, R. Ferreres, J. Flores, C. Francois, B. Fumado, V. Fung, K.S.C. Fusco, F. Gagro, A. Solis, B.G. Gaussem, P. Gayretli, Z. Gil-Herrera, J. Gatineau, A.G. Girona-Alarcon, M. Godinez, K.A.C. Goffard, J.-C. Gonzales, N. Gonzalez-Granado, L.I. Gonzalez-Montelongo, R. Guerder, A. Gulhan, B. Gumucio, V.D. Hanitsch, L.G. Gunst, J. Gut, M. Hadjadj, J. Hancerli, S. Hariyan, T. Hatipoglu, N. Heppekcan, D. Hernandez-Brito, E. Ho, P.-K. Holanda-Pena, M.S. Horcajada, J.P. Hraiech, S. Humbert, L. Hung, I.F.N. Iglesias, A.D. Inigo-Campos, A. Jamme, M. Arranz, M.J. Jimeno, M.-T. Jordan, I. Kanik-Yuksek, S. Kara, Y.B. Karahan, A. Karbuz, A. Yasar, K.K. Kasapcopur, O. Kashimada, K. Demirkol, Y.K. Kido, Y. Kizil, C. Kilic, A.O. Koutsoukou, A. Krol, Z.J. Ksouri, H. Kuentz, P. Kwan, A.M.C. Kwan, Y.W.M. Kwok, J.S.Y. Lam, D.S.Y. Lampropoulou, V. Lanternier, F. Le Bourgeois, F. Leo, Y.-S. Lopez, R.L. Levin, M. Levy, M. Levy, R. Li, Z. Lilleri, D. Lima, E.J.A.B. Linglart, A. Lopez-Collazo, E. Lorenzo-Salazar, J.M. Louapre, C. Lubetzki, C. Lung, K.-C. Lye, D.C. Magnone, C. Mansouri, D. Marchioni, E. Marioli, C. Marjani, M. Marques, L. Pereira, J.M. Martin-Nalda, A. Pueyo, D.M. Marzana, I. Mata-Martinez, C. Mathian, A. Matos, L.R.B. Matthews, G.V. Mayaux, J. McLaughlin-Garcia, R. Meersseman, P. Mege, J.-L. Mekontso-Dessap, A. Melki, I. Meloni, F. Meritet, J.-F. Merlani, P. Akcan, O.M. Mezidi, M. Migeotte, I. Millereux, M. Million, M. Mirault, T. Mircher, C. Mirsaeidi, M. Mizoguchi, Y. Modi, B.P. Mojoli, F. Moncomble, E. Melian, A.M. Martinez, A.M. Morange, P.-E. Mordacq, C. Morelle, G. Mouly, S.J. Munoz-Barrera, A. Nafati, C. Nagashima, S. Nakagama, Y. Neven, B. Neves, J.F. Ng, L.F.P. Ng, Y.-Y. Nielly, H. Medina, Y.N. Cuadros, E.N. Ocejo-Vinyals, J.G. Okamoto, K. Oualha, M. Ouedrani, A. Ozkaya-Parlakay, A. Pagani, M. Papadaki, M. Parizot, C. Parola, P. Pascreau, T. Paz-Artal, E. Pedraza, S. Pellecer, N.C.G. Pellegrini, S. De Diego, R.P. Perez-Fernandez, X.L. Philippe, A. Picod, A. De Chambrun, M.P. Piralla, A. Planas-Serra, L. Ploin, D. Poncelet, G. Poulakou, G. Pouletty, M.S. Pourshahnazari, P. Qiu-Chen, J.L. Quentric, P. Rambaud, T. Raoult, V. Rebillat, A.-S. Redin, C. Resmini, L. Ricart, P. Richard, J.-C. Rivet, N. Rocamora-Blanch, G. Rodero, M.P. Rodrigo, C. Rodriguez, L.A. Rodriguez-Palmero, A. Romero, C.S. Rothenbuhler, A. Roux, D. Rovina, N. Rozenberg, F. Ruch, Y. Ruiz, M. Del Prado, M.Y.R. Ruiz-Rodriguez, J.C. Sabater-Riera, J. Saks, K. Salagianni, M. Sanchez, O. Sanchez-Montalva, A. Sanchez-Ramon, S. Schidlowski, L. Schluter, A. Schmidt, J. Schmidt, M. Schuetz, C. Schweitzer, C.E. Scolari, F. Sediva, A. Seijo, L. Seminario, A.G. Seng, P. Senoglu, S. Seppanen, M. Llovich, A.S. Shahrooei, M. Siguret, V. Siouti, E. Smadja, D.M. Smith, N. Sobh, A. Soler, C. Sozeri, B. Stella, G.M. Stepanovskiy, Y. Stoclin, A. Taccone, F. Taupin, J.-L. Tavernier, S.J. Terrier, B. Thiery, G. Thorball, C. Thorn, K. Thumerelle, C. Tipu, I. Tolstrup, M. Tomasoni, G. Toubiana, J. Alvarez, J.T. Tsang, O.T.Y. Tserel, L. Tso, E.Y.K. Tucci, A. Oz, Ş.K.T. Ursini, M.V. Utsumi, T. Uzunhan, Y. Vabres, P. Valencia-Ramos, J. Van Den Rym, A.M. Vandernoot, I. Velez-Santamaria, V. Veliz, S.P.Z. Vidigal, M.C. Viel, S. Vilain, C. Vilaire-Meunier, M.E. Villar-Garcia, J. Vincent, A. Vogt, G. Voiriot, G. Volokha, A. Vuotto, F. Wauters, E. Wu, A.K.L. Wu, T.-C. Yahşi, A. Yesilbas, O. Yildiz, M. Young, B.E. Yukselmiş, U. Zecca, M. Zuccaro, V. Van Praet, J. Lambrecht, B.N. Van Braeckel, E. Bosteels, C. Hoste, L. Hoste, E. Bauters, F. De Clercq, J. Heijmans, C. Slabbynck, H. Naesens, L. Florkin, B. Boulanger, C. Vanderlinden, D. Allavena, C. Andrejak, C. Angoulvant, F. Azoulay, C. Bachelet, D. Bartoli, M. Basmaci, R. Behillill, S. Beluze, M. Benech, N. Benkerrou, D. Bhavsar, K. Bitker, L. Bouadma, L. Bouscambert-Duchamp, M. Paz, P.C. Cervantes-Gonzalez, M. Chair, A. Coelho, A. Cordel, H. Couffignal, C. D'Ortenzio, E. De Montmollin, E. Debard, A. Debray, M.-P. Desvallee, M. Diallo, A. Diouf, A. Dorival, C. Dubos, F. Eloy, P. Epaulard, O. Esposito-Farase, M. Etienne, M. Garot, D. Gault, N. Gaymard, A. Ghosn, J. Gigante, T. Gilg, M. Goehringer, F. Guedj, J. Hoctin, A. Hoffmann, I. Houas, I. Hulot, J.-S. Jaafoura, S. Kaguelidou, F. Kali, S. Kerroumi, Y. Khalil, A. Khan, C. Kimmoun, A. Laouenan, C. Laribi, S. Le, M. Le Bris, C. Le Gac, S. Le Hingrat, Q. Le Mestre, S. Le Nagard, H. Lemaignen, A. Lemee, V. Lescure, F.-X. Levy, Y. Lingas, G. Lucet, J.C. MacHado, M. Mambert, M. Manuel, A. Meziane, A. Mouquet, H. Mullaert, J. Neant, N. Noret, M. Papadopoulos, A. Paul, C. Peiffer-Smadja, N. Peigne, V. Petrov-Sanchez, V. Peytavin, G. Pham, H. Picone, O. Puechal, O. Rosa-Calatrava, M. Rossignol, B. Rossignol, P. Roy, C. Schneider, M. Su, R. Tardivon, C. Tellier, M.-C. Teoule, F. Terrier, O. Timsit, J.F. Tual, C. Vanel, N. Veislinger, A. Wiedemann, A. Danielson, J.J. Dobbs, K. Kashyap, A. Ding, L. Dalgard, C.L. Sottini, A. Quaresima, V. Quiros-Roldan, E. Rossi, C. Bettini, L.R. D'Angio, M. Beretta, I. Montagna, D. Licari, A. Marseglia, G.L. Storgaard, M. Jorgensen, S. Al-Muhsen, S. Al-Mulla, F. Arias, A.A. Bogunovic, D. Bolze, A. Brodin, P. Bryceson, Y. Bustamante, C.D. Butte, M.J. Chakravorty, S. Christodoulou, J. Constantinescu, S.N. Cooper, M.A. Desai, M. Drolet, B.A. El Baghdadi, J. Espinosa-Padilla, S. Froidure, A. Henrickson, S.E. Hsieh, E.W.Y. Husebye, E.S. Imai, K. Itan, Y. Jarvis, E.D. Karamitros, T. Ku, C.-L. Ling, Y. Lucas, C.L. Maniatis, T. Marodi, L. Milner, J.D. Mironska, K. Novelli, A. Novelli, G. Renia, L. Resnick, I. Sancho-Shimizu, V. Seppanen, M.R.J. Shahrooei, M. Slaby, O. Tayoun, A.A. Ramaswamy, S. Turvey, S.E. Furkan Uddin, K.M. Uddin, M.J. Von Bernuth, H. Zawadzki, P. Bigio, B. De La Chapelle, A. Chen, J. Chrabieh, M. Liu, D. Nemirowskaya, Y. Cruz, I.M. Materna, M. Pelet, S. Seeleuthner, Y. Thibault, C. Liu, Z. Foti, G. Bellani, G. Citerio, G. Contro, E. Pesci, A. Valsecchi, M.G. Cazzaniga, M. Batten, I. Reddy, C. McElheron, M. Noonan, C. Connolly, E. Fallon, A. Erikstrup, C. Pedersen, O.B. Sorensen, E. Mikkelsen, S. Dinh, K.M. Larsen, M.A.H. Paulsen, I.W. Von Stemann, J.H. Hansen, M.B. Annereau, J.-P. Briseno-Roa, L. Gribouval, O. Pelet, A. Alcover, A. Aschard, H. Bousso, P. Bruhns, P. Cerf-Bensussan, N. Cumano, A. D'Enfert, C. Deriano, L. Dillies, M.-A. Di Santo, J. Dromer, F. Eberl, G. Enninga, J. Gomperts-Boneca, I. Hasan, M. Hedestam, G.K. Hercberg, S. Ingersoll, M.A. Lantz, O. Kenny, R.A. Menager, M. Michel, F. Patin, E. Pellegrini, S. Rausell, A. Rieux-Laucat, F. Rogge, L. Fontes, M. Sakuntabhai, A. Schwartz, O. Schwikowski, B. Shorte, S. Tangy, F. Toubert, A. Touvier, M. Ungeheuer, M.-N. Zimmer, C. Albert, M.L. Van Agtmael, M. Algera, A.G. Appelman, B. Van Baarle, F. Bax, D. Beudel, M. Bogaard, H.J. Bomers, M. Bonta, P. Bos, L. Botta, M. De Brabander, J. De Bree, G. De Bruin, S. Buis, D.T.P. Bugiani, M. Bulle, E. Chouchane, O. Cloherty, A. Dijkstra, M. Dongelmans, D.A. Dujardin, R.W.G. Elbers, P. Fleuren, L. Geerlings, S. Geijtenbeek, T. Girbes, A. Goorhuis, B. Grobusch, M.P. Hafkamp, F. Hagens, L. Hamann, J. Harris, V. Hemke, R. Hermans, S.M. Heunks, L. Hollmann, M. Horn, J. Hovius, J.W. De Jong, M.D. Lim, E.H.T. Van Mourik, N. Nellen, J. Nossent, E.J. Paulus, F. Peters, E. Pina-Fuentes, D.A.I. Van Der Poll, T. Preckel, B. Prins, J.M. Raasveld, J. Reijnders, T. De Rotte, M.C.F.J. Schinkel, M. Schultz, M.J. Schrauwen, F.A.P. Schuurman, A. Schuurmans, J. Sigaloff, K. Slim, M.A. Smeele, P. Smit, M. Stijnis, C.S. Stilma, W. Teunissen, C. Thoral, P. Tsonas, A.M. Tuinman, P.R. Van Der Valk, M. Veelo, D. Volleman, C. De Vries, H. Vught, L.A. Van Vugt, M. Wouters, D. Zwinderman, A.H. Brouwer, M.C. Joost Wiersinga, W. Vlaar, A.P.J. Nadif, R. Goldberg, M. Ozguler, A. Henny, J. Lemonnier, S. Coeuret-Pellicer, M. Le Got, S. Tzourio, C. Dufouil, C. Soumare, A. Lachaize, M. Fievet, N. Flaig, A. Martin, F. Bonneaudeau, B. Cannet, D. Gallian, P. Jeanne, M. Perroquin, M. Hamzeh-Cognasse, H. CoV-Contact Cohort St James's Hospital, SARS CoV2 Interest group COVID Clinicians French COVID Cohort Study Group NIAID Immune Response to COVID Group Danish CHGE COVID Human Genetic Effort HGID Lab COVID-STORM Clinicians NH-COVAIR Study Group The Danish Blood Donor Study (DBDS) Imagine COVID-Group The Milieu Interieur Consortium Amsterdam UMC Covid-19 Biobank CONSTANCES cohort 3C-Dijon Study Cerba HealthCare Etablissement du Sang study group

Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 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 1124 deceased patients (aged 20 days to 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 individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-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 individuals 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. © 2021 The Authors, some rights reserved.

Published
2021

4. Ex vivo reactivation of BKV-specific cytotoxic T-cells for the treatment of BKV-associated disease

Author

Comoli, P, Basso, S, De Sanctis, R, Moretta, A, Botti, G, Nocera, A, DE PALMA, Raffaele, Perfumo, F, Locatelli, F, Maccario, R, Azzi, A, Ginevri, F., Comoli, P, Basso, S, De Sanctis, R, Moretta, A, Botti, G, Nocera, A, DE PALMA, Raffaele, Perfumo, F, Locatelli, F, Maccario, R, Azzi, A, and Ginevri, F.

Subjects
BKV associated diseases, T cell therapy, BKV associated disease
Published
2003

5. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) for the treatment of patients with EBV-positive relapsed nasopharingeal carcinoma

Author

Maccario, R., Locatelli, F., Siena, S., Palma, R., Carminati, O., Tagliamacco, A., Schiavo, R., Basso, S., Del Galdo, F., Labirio, M., Nocera, A., Paolo Pedrazzoli, Comoli, P., Comoli, P, Pedrazzoli, P, Nocera, A, Labirio, M, Del Galdo, F, Basso, S, Schiavo, R, Tagliamacco, A, Carminati, O, DE PALMA, Raffaele, Siena, S, Locatelli, F, and Maccario, R.

Subjects
Nasopharyngeal Carcinoma, EBV, T cell therapy
Published
2002

7. Successful generation of p190-BCR ABL-specific T-cell lines for prophylaxis/treatment of minimal residual disease in HSCT recipients with Ph+ acute lymphoblastic leukaemia

Author

Basso, S., Quartuccio, G., Guido, I., Quadrelli, C., Gurrado, A., Piantoni, L., Zavras, N., Cantoni, F., Falcone, R., Riva, Giovanni, Barozzi, Patrizia, Potenza, Leonardo, Maccario, R., Zecca, M., Luppi, Mario, and Comoli, P.

Subjects
p190-BCR ABL specific T cell lines, CTL, CTL, p190-BCR ABL specific T cell lines, Ph+ALL, Ph+ALL
Published
2012

8. Identification and characterization of Aspergillus-specific immune responses to diagnose invasive aspergillosis in high risk patients: a multicenter study

Author

Potenza, Leonardo, Vallerini, Daniela, Barozzi, Patrizia, Riva, Giovanni, Maertens, J, Candoni, A, Beauvais, A, Zanetti, Eleonora, Quadrelli, C, Morselli, M, Forghieri, Fabio, Maccaferri, M, Paolini, Ambra, Marasca, Roberto, DEL GIOVANE, Cinzia, D'Amico, Roberto, Ciceri, F, Comoli, P, Cesaro, S, Caira, M, Pagano, L, Romani, L, Narni, Franco, Latgè, Jp, and Luppi, Mario

Subjects
Elispot, Invasive aspergillosis, Elispot, Invasive aspergillosis
Published
2011

12. Current preventive strategies and management of Epstein–Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

Author

San Juan, R, Manuel, O, Hirsch, Hh, Fernández Ruiz, M, López Medrano, F, Comoli, P, Caillard, S, Grossi, P, Aguado, Jm, Álamo Martínez JM, Anaya, F, Anttila, Vj, Arnol, M, Avolio, Aw, Baccarani, U, Castello, Ib, Boletis, I, Bonofiglio, R, Viamigliori, A, Bressollette, C, Brockmann, J, Pulido, Jc, Catalán, P, Christiansen, C, Cofan, F, Cordero, E, Leiro, Mc, Dantal, J, D'Armini, A, Delgado, Jf, Dello Strologo, L, Gesu, B, DI RAIMONDO, Francesco, Dierickx, D, Eis Hübinger, A, Kremer, Sf, Faggian, G, Fariñas, Mc, Folgueira, Md, Fontana, I, Franco, A, Furian, L, Garzoni, C, Ghirardo, G, Ginevri, F, Grinyó, J, Grossi, Pa, Gupte, G, Hansson, L, Helanterä, I, Herrero, Ji, Hobin, D, Hoffmann, D, Jan, L, Jarque, I, Jespersen, B, Kaczmarek, I, Klin, G, Kevin, P, Koneth, I, Kovac, D, Lacaille, F, Lautenschlager, I, Len, O, Lladó, L, Loy, M, Maeso, Ma, Marianne, Lv, Marsh, J, Meylan, P, Miñambres, E, Montejo, M, Mueller, N, Muñoz, P, Nadalin, S, Kamar, N, Nicolas, B, Olivier, D, Palomo, J, Pascual, M, Peter, J, Pierre, F, Portero, Mf, Provot, F, Boluda, Er, Regalia, E, Reina, G, Reuter, S, Ricart, Mj, García, Mr, Rollag, H, Russo, Fp, Sabé, N, Salcedo, M, Santambrogio, L, Seeman, T, Serra, N, Sgarabotto, D, Simonek, J, Thierry, Y, Thomsen, Mk, Tihic, N, Torre Cisneros, J, Travi, G, Tulissi, P, Moal, V, Veroux, Massimiliano, Santandreu, Av, Vizzini, G, Zibar, L., Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Department of Virology, and Medicum

Subjects
Epstein-Barr Virus Infections, Cross-sectional study, Settore MED/18 - CHIRURGIA GENERALE, medicine.medical_treatment, Medizin, Epstein-Barr virus, Europe, Post-transplant lymphoproliferative disease, Pre-emptive treatment, Survey, Microbiology (medical), Infectious Diseases, medicine.disease_cause, Organ transplantation, Epstein–Barr virus, Surveys and Questionnaires, hemic and lymphatic diseases, Medicine, Tomography, TOR Serine-Threonine Kinases, Immunosuppression, General Medicine, Viral Load, pre-emptive treatment, X-Ray Computed, 3. Good health, Cross-Sectional Studies, Humans, Immunosuppressive Agents, Lymphoproliferative Disorders, Positron-Emission Tomography, Rituximab, Tomography, X-Ray Computed, Viremia, Organ Transplantation, Transplant Recipients, post-transplant lymphoproliferative disease, Viral load, medicine.drug, medicine.medical_specialty, survey, Internal medicine, business.industry, Immunology, 3111 Biomedicine, business, Solid organ transplantation, Serostatus
Abstract

There is limited clinical evidence on the utility of the monitoring of Epstein–Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients.

Published
2015
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15. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4 + T-cell subsets expressing a regulatory/suppressive phenotype

Author

Maccario, R., Podestà, M., Moretta, A., Cometa, A., Comoli, P., DANIELA MONTAGNA, Daudt, L., Ibatici, A., Piaggio, G., Pozzi, S., Frassoni, F., and Locatelli, F.

Subjects
Dendritic cells (DC), Mesenchymal stem cells (MSC), Mixed lymphocyte culture (MLC), Regulatory T-cells, Tolerance
Published
2005

21. LAKES: Long distance dispersal of aquatic key species

Author

Charalambides, I., Comoli, P., Croft, J., Figuerola, J., Gornall, R.J., Green, A.J., Hobæk, A., King, A., Lurz, P.W.W., Manca, M., Preston, C.D., Rushton, S.P., Sand, A., Sanderson, R., Santamaria, L., Schwenk, K., Shirley, M.D.F., Sutton, M.A., Moreno, J.M., Van der Putten, W.H., Struwe, S., and Plant Animal Interactions - Aquatic Ecology

Published
2000

28. Cord blood transplantation for children with acute leukemia

Author

Locatelli, F., Rocha, V., Chastang, C., Arcese, W., Ortega, J., Pasquini, R., Souillet, G., Ferreira, E., Comoli, P., and Gluckman, E.

Subjects
Acute leukemia, Cord blood transplantation, Graft versus-leukemia, Graft-versus-host disease, Leukemia relapse
Published
1998

30. RESTRICTED TCR REPERTOIRE AND LONG-TERM PERSISTENCE OF DONOR-DERIVED ANTIGEN-EXPERIENCED CD4+ T CELLS IN ALLOGENEIC BONE MARROW TRANSPLANTATION RECIPIENTS

Author

Vavassori, M., Maccario, R., Moretta, A., Comoli, P., Wack, A., Locatelli, F., Lanzavecchia, A., Maserati, E., Dellabona, P., Casorati, G., and DANIELA MONTAGNA

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Cell Survival, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Vaccination, Infant, Lymphocyte Activation, Clone Cells, Child, Preschool, Tetanus Toxoid, Immunology and Allergy, Humans, Female, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Child, Immunologic Memory, Bone Marrow Transplantation
Abstract

We investigated the contribution of transfer of Ag-experienced donor T cells to the immune reconstitution of allogeneic bone marrow transplantation (BMT) recipients. To this purpose, we used a combination of cell culture methods to isolate tetanus toxoid (TT)-specific T cell clones, and a sensitive and specific heteroduplex analysis to monitor the presence of a particular clonotype using TCR N region sequences. We document that patients after BMT display a small response to TT, entirely accounted for by few donor-derived clones. These patients show a strong polyclonal response to TT vaccination; however, the T cell clones transferred with the transplant can still be detected within the polyclonal T cell lines for up to at least 5 yr after BMT. We also demonstrate that vaccination of donors with TT before BMT results in a more relevant transfer of Ag-experienced T cells, allowing the recipients to mount a strong polyclonal response without need of vaccination. These findings provide a rationale for vaccinating donors to optimize adoptive transfer of protective T cell immunity into recipients, and suggest the possibility of using preventive T cell adoptive therapy in conjunction with marrow infusion.

Published
1996

33. ENZYME LINKED IMMUNOSPOT (ELISPOT) ASSAY FOR THE DIAGNOSIS OF INVASIVE ASPERGILLOSIS IN HIGH RISK PATIENTS

Author

Potenza, L., Barozzi, P., Vallerini, D., Maertens, J., anna candoni, Riva, G., Zanetti, E., Quadrelli, C., Bosco, R., Morselli, M., Forghieri, F., Maccaferri, M., Pedrazzi, L., Bonini, A., D Amico, R., Donelli, A., Codeluppi, M., Rossi, G., Ciceri, F., Comoli, P., Narni, F., Torelli, G., Luppi, M., Potenza, L, Barozzi, P, Vallerini, D, Maertens, J, Candoni, A, Riva, G, Zanetti, E, Quadrelli, C, Bosco, R, Morselli, M, Forghieri, F, Maccaferri, M, Pedrazzi, L, Bonini, A, D'Amico, R, Donelli, A, Codeluppi, M, Rossi, G, Ciceri, Fabio, Comoli, P, Narni, F, Torelli, G, and Luppi, M.

34. Autologous Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed nasopharingeal carcinoma

Author

Paolo Pedrazzoli, Maccario, R., Locatelli, F., Siena, S., Palma, R., Del Galdo, F., Carminati, O., Labirio, M., Moretta, A., Schiavo, R., Basso, S., Comoli, P., Comoli, P, Basso, S, Schiavo, R, Moretta, A, Labirio, M, Carminat, O, Del Galdo, F, DE PALMA, Raffaele, Siena, S, Locatelli, F, Maccario, R, and Pedrazzoli, P.

Subjects
Transplantation, Oncology, Hematology

46. IDENTIFICATION AND VALIDATION OF DIAGNOSTIC CUT-OFF VALUES FOR THE DIAGNOSIS OF INVASIVE ASPERGILLOSIS BY ELISPOT ASSAY IN HIGH RISK PATIENTS WITH HEMATOLOGIC MALIGNANCIES

Author

Forghieri, F., Vallerini, D., Barozzi, P., Lagreca, I., Riva, G., Morselli, M., Colaci, E., Paolini, A., Maccaferri, M., Coluccio, V., Cuoghi, A., Bresciani, P., Fantuzzi, V., Pioli, V., Gilioli, A., Giusti, D., Celli, M., Messerotti, A., Nasillo, V., Bettelli, F., Marasca, R., Comoli, P., Narni, F., Trenti, T., Livio PAGANO, Maertens, J., Candoni, A., Fanin, R., Viale, P. L., Lewis, R., Stanzani, M., Codeluppi, M., Mussini, C., Iughetti, L., Luppi, M., and Potenza, L.

48. Alloantigen-induced human lymphocytes rendered nonresponsive by a combination of anti-CD80 monoclonal antibodies and cyclosporin-A suppress mixed lymphocyte reaction in vitro

Author

Comoli, P., Montagna, D., Moretta, A., Marco Zecca, Locatelli, F., and Maccario, R.

Subjects
Immunology, Immunology and Allergy
Abstract

Induction of a state of long-term, alloantigen-specific T cell nonresponsiveness has significant implications for human transplantation. It has been previously described that alloantigen-specific anergy may be induced by addition of cyclosporin-A together with anti-CD80(B7-1) mAb to a MLR. In this study we endeavored to verify whether alloantigen-induced PBL rendered anergic by the addition of a combination of anti-B7 mAb and cyclosporin-A during a MLR had a suppressive effect when added to autologous lymphocytes activated in MLR. We found that: 1) the addition of cells rendered anergic by this procedure to a MLR suppress both proliferative and cytotoxic response of autologous responsive PBL to either the same or third-party stimulator cells; 2) the suppressive effect is limited to alloantigen-induced T cell activation, as addition of anergic cells does not influence mitogen- or antigen-induced proliferation of autologous responsive T cells; 3) nonresponsiveness of suppressed cells cannot be reversed by either subsequent restimulation with allogeneic cells or addition of exogenous IL-2 to the cultures; 4) the suppressive effect is apparently not due to secretion of anergic cell-derived soluble factors, but it seems to be dependent on cell-cell contact between anergic, responsive, and stimulator cells. These data suggest that: 1) the delivery of a direct signal mediated by anergic lymphocytes through a cell-cell contact is likely to be the mechanism responsible for the suppressive effect here described; 2) anergic cells may propagate alloantigen-specific tolerance to potentially responsive autologous lymphocytes. Preliminary experiments indicate that anti-CD86(B7-2) mAb may play a similar role in the generation of alloantigen-induced nonresponsiveness.

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