Hierarchical clustering uncovered disease patterns and further untangled complexities in immune complex-mediated idiopathic MPGN and C3 glomerulopathy
Year: 2025
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) is currently stratified into complement C3 glomerulopathy (C3G) and immune complex-mediated MPGN (IC-MPGN). However, classification is subject to continued debate. METHODS: Here, we applied hierarchical clustering to a much larger cohort of patients with C3G/IC-MPGN (295 individuals), extensively characterized for genetic and autoimmune complement abnormalities, with the goal of unraveling specific disease patterns. We also designed a user-friendly web application that with input of data at diagnosis could make cluster classification clinically applicable. RESULTS: Five clusters with unique phenotypic and complement profiles were identified. Cluster 1 and 2 patients showed systemic complement activation until C5. Consistently, C5 nephritic factor and anti-factor B antibodies were prevalent in these clusters. Cluster 2 was distinguished from cluster 1 for classical pathway activation markers in biopsy. Cluster 3 showed C3-restricted systemic complement activation associated with the prevalence of C3 nephritic factor. Cluster 4 and 5 patients shared a normal complement profile and intense glomerular C3 staining, consistent with solid-phase complement activation, but cluster 5 distinguished for the higher prevalence of genetic abnormalities. Cluster 4 patients had the highest incidence of kidney failure during follow-up, while cluster 1 had the best kidney prognosis. However, clusters 1 and 2 showed a high risk of post-transplant recurrence. Through our web application, we could visually compare the predicted profile of new patients with those of patients included in clustering analysis and assign these patients to different clusters. The cluster-based classification allows etiologic diagnosis of C3G/IC-MPGN and had better prognostic value than current approaches. CONCLUSIONS: Our proposed strategy may possibly guide anti-complement treatment.
Source: Kidney International
Authors: Ariela Benigni, Erica Daina, Henry Löffler-Wirth, Rossella Piras, Miriam Rigoldi, Maria Schmidt, Camillo Carrara, Roberta Donadelli, Zahra Imanifard, Caterina Mele, Marta Alberti, Maddalena Marasà, Carolina Martinatto, Elena Bresin, Sara Gamba, Lisa Quadri, Giliane Nanchen, Marina Vivarelli, Francesco Emma, Gaetano La Manna, Enrico Vidal, Andrea Pasini, Andrea Ranghino, Gabriele Donati, Enrico Verrina, Andrea Angeletti, Giuliano Brunori, Mario Giordano, Federico Alberici, Umberto Maggiore, Gabriele Malgieri, Giuseppe Remuzzi, Matteo Breno, Marina Noris, Abbate Mauro, Alberici Federico, Alberti Marta, Amar Karen, Ambrosini Andrea, Anastasi Michele, Angeletti Andrea, Antonucci Luca, Ardissino Gianluigi, Aucella Filippo, Badolato Raffele, Bainotti Serena, Baraldi Olga, Basile Federica, Basso Elisa, Bedogni Stella, Benetti Elisa, Benigni Ariela, Benvenuto Simone, Berto Ilario Mauro, Besso Luca, Biancone Luigi, Bisegna Sergio, Boccardo Paola, Bonomini Mario, Bonucchi Decenzio, Boscutti Giuliano, Bossini Nicola, Bottanelli Laura, Bove Sergio, Breno Matteo, Bresin Elena, Brugnano Rachele, Brunini Francesca, Brunori Giuliano, Buccella Nadia, Buscemi Barbara, Bussolino Stefania, Cagna Daniele, Calcaterra Eleonora, Cambareri Maria Francesco, Campolo Gesualdo, Canavese Caterina, Cantaluppi Vincenzo, Capitanini Alessandro, Carrara Camillo, Carrara Fabiola, Caruso Maria Rosa, Casartelli Donatella, Cavalli Andrea, Cesca Laura, Chirco Giuseppe, Cimino Simonetta, Cingolani Alessandra, Cirami Lino, Citterio Franco, Clari Roberta, Colturi Carla, Colussi Giacomo, Conte Ferruccio, Comai Giorgia, Cozzolino Mario Gennaro, Cravedi Paolo, Cugini Daniela, Daina Erica, Dall'Amico Roberto, Damiano Francesca, D'Amico Marco, De Amicis Sara, De Biase Consuelo, De Paolis Paolo, De Rosa Marcelo, De Sanctis Lucia Barbara, De Seigneux Sophie, Decostanzi Ester, Del Vecchio Lucia, Delbarba Elisa, Delcorso Claudia, Demetri Marcello, Di Luca Marina, Di Maso Vittorio, Di Vico Maria Cristina, Diadei Olimpia, Donadelli Roberta, Donati Gabriele, Dossi Fiorella, Dufey Teso Anne, Emma Francesco, Esposito Pasquale, Fasoli Gianluca, Federico Stefano, Fenoglio Roberta, Feriozzi Sandro, Ferrante Maria Paola, Ferrantelli Angelo, Ferrari Annachiara, Ferretti Alfonso, Ferro Michela, Fiaccadori Enrico, Fischer Maria Stephanie, Floreani Riccardo, Fotue Kamokwe Yvonne, Gallelli Beniamina, Gallo Ester, Gamba Sara, Gandolfini Ilaria, Garosi Guido, Garrone Alberto, Gennarini Alessia, Gentile Micaela, Gesualdo Loreto, Gherardi Giulia, Ghiggeri Gian Marco, Giannese Domenico, Gianoglio Bruno, Gigante Antonietta, Giordani Maria Cora, Giordano Mario, Giovanella Silvia, Giovinazzo Gloria, Gotti Eliana, Grandaliano Giuseppe, Gregorini Gina, Gregorini Marilena, Gualeni Chiara, Guarinoni Chiara, Guarnieri Andrea, Guastini Roberta, Guglielmetti Gabriele, Hadaya Karine, Haidar Fadi, Hirt-Minkowski Patricia, Huidobro Espinosa Juan Pablo, Iatropoulos Paraskevas, Imanifard Zahra, Imeraj Amantia, Infante Barbara, Inferrera Claudia, Kemper Markus, La Manna Gaetano, La Milia Vincenzo, Lambertini Domenica, Lazzarin Roberta, Leone Valentina Fanny, Lepore Marta, Livon Margherita, Lo Re Claudia, Macciò Lucia, Maffei Stefano, Maggiore Umberto, Malgieri Gabriele, Magnasco Alberto, Malkiya Youssef, Mallamaci Francesca, Malvezzi Paolo, Mancianti Nicoletta, Manenti Lucio, Manini Alessandra, Manzo Alfonsino, Marasà Maddalena, Marchetti Federico, Marengo Marita, Marinosci Alessandro, Martina Guido, Martinatto Carolina, Martinelli Daniela, Massara Carlo Maria Lorenzo, Mastrangelo Antonio, Mazzaferro Sandro, Mazzola Giuseppe, Mazzon Maurizio, Mele Caterina, Melfa Gianvincenzo, Mella Alberto, Menegotto Alberto, Mercuri Silvia, Mescia Federica, Messina Giovanni, Miglietti Nunzia, Minetti Enrico Eugenio, Mondo Elena, Monti Elena, Montini Giovanni, Montoli Alberto, Moretti Maria Ilaria, Morisi Niccolò, Morotti Annamaria, Murer Luisa, Murtas Corrado, Musetti Claudio, Nastasi Valentina, Naticchia Alessandro, Nordio Maurizio, Noris Marina, Nuzzi Francesca, Paci della Costanza Osmy, Pagani Ilaria, Palmieri Daniela, Palmisano Alessandra, Panaro Laura, Pani Antonello, Papalia Teresa, Partesano Gabriele, Pasi Alessandra, Pasini Andrea, Passler Werner, Pecoraro Carmine, Penati Francesca, Pennesi Marco, Pereira Melissa, Perencin Brigitta, Perna Alessandra Fortunata, Perticucci Elena, Peruzzi Licia, Piccoli Giorgina B, Piccolo Tiziana, Piras Rossella, Pisani Antonio, Plati Anna Rita, Pollastro Rosa Maria, Portalupi Valentina, Prandini Silvia, Prolio Marta, Quadri Lisa, Rampino Teresa, Ranghino Andrea, Remuzzi Giuseppe, Rigoldi Miriam, Rizzo Paola, Rizzolo Monica, Roccatello Dario, Rolla Davide, Romagnani Paola, Romanini Dino, Roperto Rosa Maria, Rossi Natalia, Rotondi Silverio, Rubis Nadia, Ruggenenti Piero, Sabadini Ettore, Santoro Domenico, Santostefano Marisa, Scarpioni Roberto, Sciri Raffaela, Scolari Francesco, Scotti Lucia, Silecchia Valeria, Sinico Renato Alberto, Sottini Laura, Stallone Giovanni, Stea Emma Diletta, Stucchi Nadia, Tabbì Maria Grazia, Tamagnone Michela, Timio Francesca, Tognarelli Giuliana, Tommasoni Isabella, Tondolo Francesco, Torres Diletta Domenica, Toumasi Elpida, Trezzi Matteo, Trillini Matias, Tsygin Alexei, Valenza Laura, Vari Maria Rosaria, Verrina Enrico, Vezzoli Giuseppe, Viazzi Francesca, Vidal Enrico, Vitale Corrado, Vivarelli Marina, Zanella Monica
Institutions: Mario Negri Institute for Pharmacological Research, Leipzig University, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Bambino Gesù Children's Hospital, University of Padua, Azienda Ospedale - Università Padova, University of Bologna, Azienda Ospedaliero-Universitaria delle Marche, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Istituto Giannina Gaslini, Ospedale Santa Chiara, Provincia Autonoma di Trento, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, Ospedale Pediatrico Giovanni XXIII, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, University of Parma, Ospedale di Parma, Santobono Children's Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
OpenAlex ID: W4415015468