title: Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection.
abstract: Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p< 0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p< 0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease.
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Roberta
authors.identifier: 0000-0001-9507-9126
authors.initials: R
authors.lastname: Rizzo
authors.affiliation: Operative Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Gabrielli
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Bortolotti
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gentili
authors.affiliation: Operative Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piccirilli
authors.affiliation: Operative Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Chiereghin
authors.affiliation: Operative Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pavia
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolzani
authors.affiliation: Operative Unit of Obstetrics and Prenatal Medicine, Department of Medical and Surgical Sciences, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Operative Unit of Obstetrics and Prenatal Medicine, Department of Medical and Surgical Sciences, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Simonazzi
authors.affiliation: Operative Unit of Obstetrics and Prenatal Medicine, Department of Medical and Surgical Sciences, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cervi
authors.affiliation: Operative Unit of Neonatology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Capretti
authors.affiliation: Operative Unit of Neuroradiology, Careggi University Hospital, Firenze, Italy.
authors.forename: Enrico
authors.identifier: 0000-0003-0477-724X
authors.initials: E
authors.lastname: Fainardi
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Dario Di
authors.initials: DD
authors.lastname: Luca
authors.affiliation: Operative Unit of Clinical Microbiology, Department of Specialised, Experimental, and Diagnostic Medicine, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Landini
authors.affiliation: Operative Unit of Clinical Microbiology, Department of Specialised, Experimental, and Diagnostic Medicine, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
mesh_terms: D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000276:immunology* / Q000821:virology; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology*; D005865:Gestational Age; D059951:HLA-G Antigens / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000097:blood / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D059951:HLA-G Antigens; D001613:beta 2-Microglobulin