Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation
نویسندگان
چکیده
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.
منابع مشابه
Assessment of Cyclosporine Serum Concentrations on the Incidence of Acute Graft versus Host Disease Post Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for hematological disorders. Cyclosporine (CsA) is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. 103 adult patients rece...
متن کاملTreatment of chronic cutaneous graft versus host disease (GVHD) with photochemotherapy with Psoralen (PUVA): A report of five cases
Chronic graft versus host disease (GVHD) remains the most common late complication of allogenic stem cell transplantation and the most frequent cause of morbidity and mortality in these patients. To control this condition, immunosuppressive drugs are usually administered at a high dose and for a long time, which may result in several side effects. 5 patients with clinically and histopathologica...
متن کاملEvaluation of Serum Interleukin-21 and HLA-C1 Polymorphism in Pediatrician Hematopoietic Stem Cell Transplantation for Early Diagnosis of Acute Graft-Versus-Host Disease
Background: Allogenic hematopoietic stem cell transplantation (HSCT) is a strategy used for treatment of different malignant diseases. However, success of allo-HSCT can be hampered by graft-versus-host-disease (GVHD). Natural killer (NK) cells may play an important role in activating antigen presenting cells and subsequent activation of T cells. The main purpose of this study was the evaluation...
متن کاملAssessment of Cyclosporine Serum Concentrations on the Incidence of Acute Graft versus Host Disease Post Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for hematological disorders. Cyclosporine (CsA) is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. 103 adult patients rece...
متن کاملنقش اینترلوکین-18 و پذیرنده اینترلوکین-2 در بیماری حاد پیوند علیه میزبان پس از پیوند مغز استخوان
Background: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease (aGVHD). The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after BMT would be extremely val...
متن کامل