Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
| Autor: | Claudia Cappuzzello, Erica Dander, Roberto Leone, Andrea Biondi, Attilio Rovelli, Fabio Pasqualini, Paola Quarello, Matteo Parma, Fabio Pagni, Fabio Pavan, Paola De Lorenzo, Barbara Bottazzi, Cecilia Garlanda, Giovanna D'Amico, Franco Locatelli, Sonia Bonanomi, Giovanni Salvatori, Paola Vinci, Marina Sironi, Ivan Cuccovillo, Alberto Mantovani, Maria Grazia Valsecchi, Francesca Masciocchi, Franca Fagioli, Adriana Balduzzi, Elisabetta Terruzzi, Giulia Prunotto |
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| Přispěvatelé: | Dander, E, 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, Rovelli, A, D'Amico, G |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Time Factors medicine.medical_treatment Drug Resistance Graft vs Host Disease Hematopoietic stem cell transplantation Disease Inbred C57BL Gastroenterology Severity of Illness Index Mice Adrenal Cortex Hormones Prospective Studies Child Inbred BALB C Mice Inbred BALB C Hematology biology Research Paper: Immunology Age Factors Hematopoietic Stem Cell Transplantation Up-Regulation Serum Amyloid P-Component surgical procedures operative C-Reactive Protein Treatment Outcome Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA Italy Oncology Pediatric haematopoietic stem cell transplantation Child Preschool Biomarker (medicine) Female Immunology and microbiology section Homologous medicine.medical_specialty Adolescent Acute graft-versus-host disease Biomarkers Immune response Immunity Pentraxin 3 (PTX3) Animals Disease Models Animal Humans Mice Inbred C57BL Predictive Value of Tests Transplantation Homologous Young Adult 03 medical and health sciences Internal medicine Severity of illness medicine Preschool Transplantation business.industry Animal C-reactive protein acute graft-versus-host disease biomarkers hematology immune response immunity immunology and microbiology section pediatric haematopoietic stem cell transplantation pentraxin 3 (PTX3) Biomarker medicine.disease 030104 developmental biology Graft-versus-host disease Immunology Disease Models biology.protein business |
| Zdroj: | Oncotarget |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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