Dataset Information

Nano-LC-MS/MS proteomics in amniotic fluid from CAKUT patients

ABSTRACT: The objective of the present work was to identify new renal proteins responsible for Congenital Anomalies of the Kidney and of the Urinary Tract (CAKUT pathophysiology). We conducted a comparative LC-MS/MS-based proteomics analysis of amniotic fluids (AF) collected from non-severe CAKUT (ns-CAKUT; n=19), severe CAKUT (s-CAKUT; n=14), and healthy controls (cont; n=22) fetuses. We identified a total of 224 gestational age independent proteins that were significantly different in abundance when comparing (one-way ANOVA corrected p<0.05) the 3 groups of amniotic fluids 2 by 2. We identified 8 gestational-age independent proteins that were in common when comparing the 3 groups two by two, and that were considered as associated to both CAKUT onset and CAKUT severity.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Amniotic Fluid, Embryonic Stem Cell

DISEASE(S): Cakut

SUBMITTER: Mylène CAMUS

LAB HEAD: Joost-Peter Schanstra

PROVIDER: PXD022926 | Pride | 2023-09-26

REPOSITORIES: Pride

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Publications

Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity.

Fédou Camille C Camus Mylène M Lescat Ophélie O Feuillet Guylène G Mueller Ilka I Ross Bryony B Buléon Marie M Neau Eric E Alves Melinda M Goudounéche Dominique D Breuil Benjamin B Boizard Franck F Bardou Quentin Q Casemayou Audrey A Tack Ivan I Dreux Sophie S Batut Julie J Blader Patrick P Burlet-Schiltz Odile O Decramer Stéphane S Wirth Brunhilde B Klein Julie J Saulnier-Blache Jean Sébastien JS Buffin-Meyer Bénédicte B Schanstra Joost P JP

The Journal of pathology 20210616 5

Congenital anomalies of the kidney and the urinary tract (CAKUT) are the first cause of chronic kidney disease in childhood. Several genetic and environmental origins are associated with CAKUT, but most pathogenic pathways remain elusive. Considering the amniotic fluid (AF) composition as a proxy for fetal kidney development, we analyzed the AF proteome from non-severe CAKUT (n = 19), severe CAKUT (n = 14), and healthy control (n = 22) fetuses using LC-MS/MS. We identified 471 significant protei ...[more]

PMID: 33987838

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Project 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

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