Evidence map›Paper›PMID 36206263›Full record

ArticlePloS one2022

Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with CNS inflammation in children.

Frederik Ricken, Ahu Damla Can, Steffen Gräber, Martin Häusler, Willi Jahnen-Dechent

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Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Frederik RickenDivision of Neuropediatrics and Social Pediatrics, Department of Pediatrics, RWTH Aachen University Hospital, Aachen, Germany.ORCID 0000-0002-4256-5451
Ahu Damla CanDivision of Neuropediatrics and Social Pediatrics, Department of Pediatrics, RWTH Aachen University Hospital, Aachen, Germany.
Steffen GräberHelmholtz Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Hospital, Aachen, Germany.
Martin HäuslerDivision of Neuropediatrics and Social Pediatrics, Department of Pediatrics, RWTH Aachen University Hospital, Aachen, Germany.
Willi Jahnen-DechentHelmholtz Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Hospital, Aachen, Germany.ORCID 0000-0003-1315-4407
Universitätsklinikum Aachen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fetuin-A is a liver derived plasma protein showing highest serum concentrations in utero, preterm infants, and neonates. Fetuin-A is also present in cerebrospinal fluid (CSF). The origin of CSF fetuin-A, blood-derived via the blood-CSF barrier or synthesized intrathecally, is presently unclear. Fetuin-A prevents ectopic calcification by stabilizing calcium and phosphate as colloidal calciprotein particles mediating their transport and clearance. Thus, fetuin-A plays a suppressive role in inflammation. Fetuin-A is a negative acute-phase protein under investigation as a biomarker for multiple sclerosis (MS). Here we studied the association of pediatric inflammatory CNS diseases with fetuin-A glycosylation and phosphorylation. Paired blood and CSF samples from 66 children were included in the study. Concentration measurements were performed using a commercial human fetuin-A/AHSG ELISA. Of 60 pairs, 23 pairs were analyzed by SDS-PAGE following glycosidase digestion with PNGase-F and Sialidase-AU. Phosphorylation was analyzed in 43 pairs by Phos-TagTM acrylamide electrophoresis following alkaline phosphatase digestion. Mean serum and CSF fetuin-A levels were 0.30 ± 0.06 mg/ml and 0.644 ± 0.55 μg/ml, respectively. This study showed that serum fetuin-A levels decreased in inflammation corroborating its role as a negative acute-phase protein. Blood-CSF barrier disruption was associated with elevated fetuin-A in CSF. A strong positive correlation was found between the CSF fetuin-A/serum fetuin-A quotient and the CSF albumin/serum albumin quotient, suggesting predominantly transport across the blood-CSF barrier rather than intrathecal fetuin-A synthesis. Sialidase digestion showed increased asialofetuin-A levels in serum and CSF samples from children with neuroinflammatory diseases. Desialylation enhanced hepatic fetuin-A clearance via the asialoglycoprotein receptor thus rapidly reducing serum levels during inflammation. Phosphorylation of fetuin-A was more abundant in serum samples than in CSF, suggesting that phosphorylation may regulate fetuin-A influx into the CNS. These results may help establish Fetuin-A as a potential biomarker for neuroinflammatory diseases.

Indexed as

alpha-2-HS-GlycoproteinCalciumAcrylamidesAcute-Phase ProteinsAlkaline Phosphatasealpha-FetoproteinsAsialoglycoprotein ReceptorBiomarkersCentral Nervous System DiseasesChildGlycosylationHumansInfant, NewbornInfant, PrematureInflammationLiverAcrylamidesAcute-Phase ProteinsAlkaline Phosphatasealpha-2-HS-Glycoproteinalpha-FetoproteinsAsialoglycoprotein ReceptorBiomarkersCalciumNeuraminidasePhosphatesSerum Albumin

Identifiers

PMID36206263
PMCPMC9544022
OpenAlexW4303519745

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.