PXD029105-1

PXD029105 is an original dataset announced via ProteomeXchange.

Title	Identification of new amniotic fluid prognostic biomarkers of congenital cytomegalovirus infection severity
Description	Background: Congenital cytomegalovirus (cCMV) is a common intrauterine infection, leading to neurodevelopmental disabilities. Early prognostic assessment of the severity of cCMV has remained an ongoing challenge. We aimed to identify amniotic fluid biomarkers of the severity of cCMV-related fetal brain injury. Methods: Global proteome analysis was performed in mid-gestation amniotic fluid samples, comparing fetuses with severe cCMV to asymptomatic CMV-infected fetuses (the discovery cohort). The levels of selected differentially-excreted proteins were further determined by specific immunoassays, and evaluated in an independent validation cohort, including clinically-blinded amniotic fluid of CMV-infected fetuses from unrelated centers. Findings: Proteome analysis identified 29 amniotic fluid proteins with distinct abundance in fetuses with severe-, compared to asymptomatic, cCMV. Pathway analysis of the differentially-excreted proteins revealed enriched pathways of inflammatory response, cellular compromise, immunological disease, organismal injury, and neurological disease, underlining a link between excessive inflammation at the maternal-fetal interface and the development of cCMV-related fetal brain damage. Importantly, the levels of two of these proteins, chemerin and galectin-3-binding protein (Gal-3BP), selected for validation, demonstrated 88.2% sensitivity (each), 100-96.2% specificity, 100-93.8% positive predictive value, and 92.9-92.6% negative predictive value, with 0.98-0.97 area under the curve (for chemerin - Gal-3BP, respectively) in differentiating 17 fetuses with severe cCMV from 26 asymptomatic CMV-infected fetuses. Interpretation: These results identify the immunomodulatory proteins chemerin and Gal-3BP as new highly predictive amniotic fluid biomarkers of cCMV severity, which could guide early prognostic stratification and potential personalized treatment of cCMV-infected fetuses. Funding: Israel Science Foundation; Research Fund of the Hadassah Medical Organization
HostingRepository	PRIDE
AnnounceDate	2022-05-25
AnnouncementXML	Submission_2022-05-25_01:54:24.366.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meital Kupervaser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Cytomegalovirus sp.; NCBI TaxID: 2510939;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-13 04:23:23	ID requested
⏵ 1	2022-05-25 01:54:24	announced
2	2023-11-14 08:53:40	announced	2023-11-14: Updated project metadata.

10.1172/JCI157415;

submitter keyword: Cytomegalovirus

Congenital cytomegalovirus infection

Amniotic fluid biomarkers

Dana Wolf
contact affiliation	Ted and Frances Chanock Chair in Virology Head, Clinical Virology Unit Dept. of clinical Microbiology & Infectious Diseases Hadassah University Hospital Jerusalem, Israel 91120
contact email	dana.wolf@ekmd.huji.ac.il
lab head
Meital Kupervaser
contact affiliation	Weizmann Institute of Science
contact email	meital.kupervaser@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029105
     1. Label: PRIDE project
     2. Name: Identification of new amniotic fluid prognostic biomarkers of congenital cytomegalovirus infection severity