AUTHOR=Campos Cláudia F. , Leite Luís , Pereira Paulo , Vaz Carlos Pinho , Branca Rosa , Campilho Fernando , Freitas Fátima , Ligeiro Dário , Marques António , Torrado Egídio , Silvestre Ricardo , Lacerda João F. , Campos Jr. António , Cunha Cristina , Carvalho Agostinho 

TITLE=PTX3 Polymorphisms Influence Cytomegalovirus Reactivation After Stem-Cell Transplantation

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00088

DOI=10.3389/fimmu.2019.00088

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> 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 <italic>PTX3</italic> locus influences the risk of CMV infection is currently unknown.</p><p><bold>Methods:</bold> To dissect the contribution of genetic variation within <italic>PTX3</italic> to the development of CMV infection, we analyzed described loss-of-function variants at the <italic>PTX3</italic> locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation.</p><p><bold>Results:</bold> We report that the donor, but not recipient, h2/h2 haplotype in <italic>PTX3</italic> 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.</p><p><bold>Conclusions:</bold> Our findings demonstrate the important contribution of genetic variation in donor <italic>PTX3</italic> to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor <italic>PTX3</italic> to predict risk of CMV reactivation in this clinical setting.</p>