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 acutephase 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 therapyunresponsive 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.

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, E.; De Lorenzo, P.; Bottazzi, B.; Quarello, P.; Vinci, P.; Balduzzi, A.; Masciocchi, F.; Bonanomi, S.; Cappuzzello, C.; Prunotto, G.; Pavan, F.; Pasqualini, F.; Sironi, M.; Cuccovillo, I.; Leone, R.; Salvatori, G.; Parma, M.; Terruzzi, E.; Pagni, F.; Locatelli, F.; Mantovani, A.; Fagioli, F.; Biondi, A.; Garlanda, C.; Valsecchi, M. G.; Rovelli, A.; D'Amico, G.. - In: ONCOTARGET. - ISSN 1949-2553. - 7:50(2016), pp. 82123-82138. [10.18632/oncotarget.13488]

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

Locatelli F.;
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 acutephase 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 therapyunresponsive 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.
2016
acute graft-versus-host disease; biomarkers; hematology; immune response; immunity; immunology and microbiology section; pediatric haematopoietic stem cell transplantation; pentraxin 3 (PTX3)
01 Pubblicazione su rivista::01a Articolo in rivista
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, E.; De Lorenzo, P.; Bottazzi, B.; Quarello, P.; Vinci, P.; Balduzzi, A.; Masciocchi, F.; Bonanomi, S.; Cappuzzello, C.; Prunotto, G.; Pavan, F.; Pasqualini, F.; Sironi, M.; Cuccovillo, I.; Leone, R.; Salvatori, G.; Parma, M.; Terruzzi, E.; Pagni, F.; Locatelli, F.; Mantovani, A.; Fagioli, F.; Biondi, A.; Garlanda, C.; Valsecchi, M. G.; Rovelli, A.; D'Amico, G.. - In: ONCOTARGET. - ISSN 1949-2553. - 7:50(2016), pp. 82123-82138. [10.18632/oncotarget.13488]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1487566
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