Evidence map›Paper›PMID 35987516›Full record

ArticleEuropean journal of immunology2022

Novel homozygous CD46 variant with C-isoform expression affects C3b inactivation in atypical hemolytic uremic syndrome.

Vivien R Schack, Morten K Herlin, Henrik Pedersen, J Magnus Bernth Jensen, Mia Faerch, Bettina Bundgaard, Rasmus K Jensen, Uffe B Jensen, Rikke Christensen, Gregers R Andersen and 2 more

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In one paragraph

Article in European journal of immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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

12 authors at 2 institutions in 1 country.

Vivien R SchackDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0002-1365-3938
Morten K HerlinDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.ORCID 0000-0001-7179-4643
Henrik PedersenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
J Magnus Bernth JensenDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus N, Denmark.
Mia FaerchDepartment of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus N, Denmark.
Bettina BundgaardDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Rasmus K JensenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Uffe B JensenDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.
Rikke ChristensenDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark.
Gregers R AndersenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Steffen ThielDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.
Per HöllsbergDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0001-5314-5818
Aarhus University · DKAarhus University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy that may lead to organ failure. Dysregulation of the complement system can cause aHUS, and various disease-related variants in the complement regulatory protein CD46 are described. We here report a pediatric patient with aHUS carrying a hitherto unreported homozygous variant in CD46 (NM_172359.3:c.602C>T p.(Ser201Leu)). In our functional analyses, this variant caused complement dysregulation through three separate mechanisms. First, CD46 surface expression on the patient's blood cells was significantly reduced. Second, stably expressing CD46(Ser201Leu) cells bound markedly less to patterns of C3b than CD46 WT cells. Third, the patient predominantly expressed the rare isoforms of CD46 (C dominated) instead of the more common isoforms (BC dominated). Using BC1 and C1 expressing cell lines, we found that the C1 isoform bound markedly less C3b than the BC1 isoform. These results highlight the coexistence of multiple mechanisms that may act synergistically to disrupt CD46 function during aHUS development.

Indexed as

Atypical Hemolytic Uremic SyndromeChildComplement C3bComplement System ProteinsHumansMembrane Cofactor ProteinMutationProtein IsoformsCD46 protein, humanComplement C3bComplement System ProteinsMembrane Cofactor ProteinProtein Isoformsatypical hemolytic syndromeC3bCD46 C-isoformCD46 variant

Identifiers

PMID35987516
PMCPMC9804674
OpenAlexW4292806379

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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.