Oncotarget

Research Papers: Immunology:

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, Paola De Lorenzo, Barbara Bottazzi, Paola Quarello, Paola Vinci, Adriana Balduzzi, Francesca Masciocchi, Sonia Bonanomi, Claudia Cappuzzello, Giulia Prunotto, Fabio Pavan, Fabio Pasqualini, Marina Sironi, Ivan Cuccovillo, Roberto Leone, Giovanni Salvatori, Matteo Parma, Elisabetta Terruzzi, Fabio Pagni, Franco Locatelli, Alberto Mantovani, Franca Fagioli, Andrea Biondi, Cecilia Garlanda, Maria Grazia Valsecchi, Attilio Rovelli and Giovanna D’Amico _

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Oncotarget. 2016; 7:82123-82138. https://doi.org/10.18632/oncotarget.13488

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Abstract

Erica Dander1, Paola De Lorenzo2, Barbara Bottazzi3, Paola Quarello4, Paola Vinci1, Adriana Balduzzi5, Francesca Masciocchi5, Sonia Bonanomi5, Claudia Cappuzzello1, Giulia Prunotto5, Fabio Pavan5, Fabio Pasqualini3, Marina Sironi3, Ivan Cuccovillo3, Roberto Leone3, Giovanni Salvatori6, Matteo Parma7, Elisabetta Terruzzi7, Fabio Pagni8, Franco Locatelli9, Alberto Mantovani3,10, Franca Fagioli4, Andrea Biondi1,5, Cecilia Garlanda3, Maria Grazia Valsecchi2, Attilio Rovelli5 and Giovanna D’Amico1

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.


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