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.
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.
authors.affiliation: "M. Tettamanti" Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Dander
authors.affiliation: Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: Pediatric Onco-Haematology, City of Science and Health of Turin, Regina Margherita Children's Hospital, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Quarello
authors.affiliation: "M. Tettamanti" Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vinci
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Balduzzi
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Masciocchi
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonanomi
authors.affiliation: "M. Tettamanti" Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappuzzello
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Prunotto
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pavan
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cuccovillo
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Leone
authors.affiliation: Sigma-tau S.p.A., Department of R&D, Biotechnology, San Gerardo Hospital, Monza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Salvatori
authors.affiliation: Haematology Division and BMT Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Parma
authors.affiliation: Haematology Division and BMT Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Terruzzi
authors.affiliation: Department of Surgery and Interdisciplinary Medicine, University Milano-Bicocca, Section of Pathology, San Gerardo Hospital, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagni
authors.affiliation: Department of Pediatric Haematology-Oncology, IRCCS, Bambino Gesù Children Hospital, Roma-Department of Pediatric Science, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.|Humanitas University, Rozzano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Pediatric Onco-Haematology, City of Science and Health of Turin, Regina Margherita Children's Hospital, Torino, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: "M. Tettamanti" Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy.|Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.affiliation: Clinica Pediatrica Ospedale S. Gerardo, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Rovelli
authors.affiliation: "M. Tettamanti" Research Center, Pediatric Department, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Amico
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007558:Italy; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011237:Predictive Value of Tests; D011446:Prospective Studies; D000683:Serum Amyloid P-Component / Q000032:analysis*; D012720:Severity of Illness Index; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult; D000099153:Pentraxins
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Immune response; Immunity; Immunology and Microbiology Section; acute graft-versus-host disease; biomarkers; hematology; pediatric haematopoietic stem cell transplantation; pentraxin 3 (PTX3)