Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

// Erica Dander 1 , Paola De Lorenzo 2 , Barbara Bottazzi 3 , Paola Quarello 4 , Paola Vinci 1 , Adriana Balduzzi 5 , Francesca Masciocchi 5 , Sonia Bonanomi 5 , Claudia Cappuzzello 1 , Giulia Prunotto 5 , Fabio Pavan 5 , Fabio Pasqualini 3 , Marina Sironi 3 , Ivan Cuccovillo 3 , Roberto Leone 3 , Giovanni Salvatori 6 , Matteo Parma 7 , Elisabetta Terruzzi 7 , Fabio Pagni 8 , Franco Locatelli 9 , Alberto Mantovani 3,10 , Franca Fagioli 4 , Andrea Biondi 1,5 , Cecilia Garlanda 3 , Maria Grazia Valsecchi 2 , Attilio Rovelli 5 and Giovanna D’Amico 1 1 “M. Tettamanti” Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy 2 Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy 3 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy 4 Pediatric Onco-Haematology, City of Science and Health of Turin, Regina Margherita Children’s Hospital, Torino, Italy 5 Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy 6 Sigma-tau S.p.A., Department of R&D, Biotechnology, San Gerardo Hospital, Monza, Italy 7 Haematology Division and BMT Unit, San Gerardo Hospital, Monza, Italy 8 Department of Surgery and Interdisciplinary Medicine, University Milano-Bicocca, Section of Pathology, San Gerardo Hospital, Monza, Italy 9 Department of Pediatric Haematology-Oncology, IRCCS, Bambino Gesù Children Hospital, Roma-Department of Pediatric Science, University of Pavia, Pavia, Italy 10 Humanitas University, Rozzano, Italy Correspondence to: Giovanna D’Amico, email: // Andrea Biondi , email: // Keywords : acute graft-versus-host disease, pentraxin 3 (PTX3), biomarkers, pediatric haematopoietic stem cell transplantation, hematology, Immunology and Microbiology Section, Immune response, Immunity Received : September 22, 2016 Accepted : November 15, 2016 Published : November 21, 2016 Abstract Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapy-unresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients.