PTX3 Polymorphisms Influence Cytomegalovirus Reactivation After Stem-Cell Transplantation

Autor: Cláudia F. Campos, Luís Leite, Paulo Pereira, Carlos Pinho Vaz, Rosa Branca, Fernando Campilho, Fátima Freitas, Dário Ligeiro, António Marques, Egídio Torrado, Ricardo Silvestre, João F. Lacerda, António Campos Jr., Cristina Cunha, Agostinho Carvalho
Přispěvatelé: Repositório da Universidade de Lisboa, Universidade do Minho
Rok vydání: 2018
Předmět:
0301 basic medicine
Human cytomegalovirus
Male
Medicina Básica [Ciências Médicas]
Cytomegalovirus
Mice
0302 clinical medicine
Gene Frequency
single nucleotide polymorphism
Immunology and Allergy
stem-cell transplantation
Original Research
Hematopoietic Stem Cell Transplantation
virus diseases
PTX3
Middle Aged
3. Good health
Serum Amyloid P-Component
C-Reactive Protein
Ciências Médicas::Medicina Básica
Cytomegalovirus Infections
Female
Stem cell
lcsh:Immunologic diseases. Allergy
Adult
Risk
Adolescent
Genotype
precision medicine
Immunology
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
03 medical and health sciences
Young Adult
Genetic variation
medicine
genomics
Animals
Humans
Transplantation
Homologous
Genetic Predisposition to Disease
cytomegalovirus
Genetic Association Studies
Science & Technology
Portugal
business.industry
Haplotype
medicine.disease
Transplantation
030104 developmental biology
Virus Activation
lcsh:RC581-607
Serostatus
business
030215 immunology
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Vol 10 (2019)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 1664-3224
Popis: Copyright © 2019 Campos, Leite, Pereira, Vaz, Branca, Campilho, Freitas, Ligeiro, Marques, Torrado, Silvestre, Lacerda, Campos, Cunha and Carvalho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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.
This work was supported by the 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).
Databáze: OpenAIRE
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