Author(s):
Campos, Cláudia F. ; Leite, Luís ; Pereira, Paulo ; Vaz, Carlos Pinho ; Branca, Rosa ; Campilho, Fernando ; Freitas, Fátima ; Ligeiro, Dário ; Marques, António ; Torrado, Egídio ; Silvestre, Ricardo Jorge Leal ; Lacerda, João F. ; Campos Jr., António ; Cunha, Cristina ; Carvalho, Agostinho
Date: 2019
Persistent ID: http://hdl.handle.net/1822/62289
Origin: RepositóriUM - Universidade do Minho
Subject(s): cytomegalovirus; stem-cell transplantation; PTX3; single nucleotide polymorphism; precision medicine; genomics; Science & Technology; Ciências Médicas::Medicina Básica
Description
Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown. Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation. Results: We report that the donor, but not recipient, h2/h2 haplotype in PTX3 increased the risk of CMV reactivation after 24 months following transplantation, with a significant effect on survival. Among recipients with h2/h2 donors, CMV seropositive patients as well as those receiving grafts from unrelated donors, regardless of the CMV serostatus, were more prone to develop viral reactivation after transplantation. Most importantly, the h2/h2 haplotype was demonstrated to display an influence toward risk of CMV reactivation comparable to that conferred by the unrelated status of the donor alone. Conclusions: Our findings demonstrate the important contribution of genetic variation in donor PTX3 to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor PTX3 to predict risk of CMV reactivation in this clinical setting.
Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (SFRH/BPD/96176/2013 to CC, IF/01390/2014 to ET, IF/00021/2014 to RS, and IF/00735/2014 to AgC)
