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

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 a...

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Autores principales: Dander, Erica, De Lorenzo, Paola, Bottazzi, Barbara, Quarello, Paola, Vinci, Paola, Balduzzi, Adriana, Masciocchi, Francesca, Bonanomi, Sonia, Cappuzzello, Claudia, Prunotto, Giulia, Pavan, Fabio, Pasqualini, Fabio, Sironi, Marina, Cuccovillo, Ivan, Leone, Roberto, Salvatori, Giovanni, Parma, Matteo, Terruzzi, Elisabetta, Pagni, Fabio, Locatelli, Franco, Mantovani, Alberto, Fagioli, Franca, Biondi, Andrea, Garlanda, Cecilia, Valsecchi, Maria Grazia, Rovelli, Attilio, D'Amico, Giovanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347680/
https://www.ncbi.nlm.nih.gov/pubmed/27893415
http://dx.doi.org/10.18632/oncotarget.13488
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author Dander, Erica
De Lorenzo, Paola
Bottazzi, Barbara
Quarello, Paola
Vinci, Paola
Balduzzi, Adriana
Masciocchi, Francesca
Bonanomi, Sonia
Cappuzzello, Claudia
Prunotto, Giulia
Pavan, Fabio
Pasqualini, Fabio
Sironi, Marina
Cuccovillo, Ivan
Leone, Roberto
Salvatori, Giovanni
Parma, Matteo
Terruzzi, Elisabetta
Pagni, Fabio
Locatelli, Franco
Mantovani, Alberto
Fagioli, Franca
Biondi, Andrea
Garlanda, Cecilia
Valsecchi, Maria Grazia
Rovelli, Attilio
D'Amico, Giovanna
author_facet Dander, Erica
De Lorenzo, Paola
Bottazzi, Barbara
Quarello, Paola
Vinci, Paola
Balduzzi, Adriana
Masciocchi, Francesca
Bonanomi, Sonia
Cappuzzello, Claudia
Prunotto, Giulia
Pavan, Fabio
Pasqualini, Fabio
Sironi, Marina
Cuccovillo, Ivan
Leone, Roberto
Salvatori, Giovanni
Parma, Matteo
Terruzzi, Elisabetta
Pagni, Fabio
Locatelli, Franco
Mantovani, Alberto
Fagioli, Franca
Biondi, Andrea
Garlanda, Cecilia
Valsecchi, Maria Grazia
Rovelli, Attilio
D'Amico, Giovanna
author_sort Dander, Erica
collection PubMed
description 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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spelling pubmed-53476802017-03-31 Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation Dander, Erica De Lorenzo, Paola Bottazzi, Barbara Quarello, Paola Vinci, Paola Balduzzi, Adriana Masciocchi, Francesca Bonanomi, Sonia Cappuzzello, Claudia Prunotto, Giulia Pavan, Fabio Pasqualini, Fabio Sironi, Marina Cuccovillo, Ivan Leone, Roberto Salvatori, Giovanni Parma, Matteo Terruzzi, Elisabetta Pagni, Fabio Locatelli, Franco Mantovani, Alberto Fagioli, Franca Biondi, Andrea Garlanda, Cecilia Valsecchi, Maria Grazia Rovelli, Attilio D'Amico, Giovanna Oncotarget Research Paper: Immunology 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. Impact Journals LLC 2016-11-21 /pmc/articles/PMC5347680/ /pubmed/27893415 http://dx.doi.org/10.18632/oncotarget.13488 Text en Copyright: © 2016 Dander et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Immunology
Dander, Erica
De Lorenzo, Paola
Bottazzi, Barbara
Quarello, Paola
Vinci, Paola
Balduzzi, Adriana
Masciocchi, Francesca
Bonanomi, Sonia
Cappuzzello, Claudia
Prunotto, Giulia
Pavan, Fabio
Pasqualini, Fabio
Sironi, Marina
Cuccovillo, Ivan
Leone, Roberto
Salvatori, Giovanni
Parma, Matteo
Terruzzi, Elisabetta
Pagni, Fabio
Locatelli, Franco
Mantovani, Alberto
Fagioli, Franca
Biondi, Andrea
Garlanda, Cecilia
Valsecchi, Maria Grazia
Rovelli, Attilio
D'Amico, Giovanna
Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title_full Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title_fullStr Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title_full_unstemmed Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title_short Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
title_sort pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
topic Research Paper: Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347680/
https://www.ncbi.nlm.nih.gov/pubmed/27893415
http://dx.doi.org/10.18632/oncotarget.13488
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