Evidence map›Paper›PMID 30533526›Full record

ArticleNeurology. Genetics2018

Molecular pathogenesis of human CD59 deficiency.

Netanel Karbian, Yael Eshed-Eisenbach, Adi Tabib, Hila Hoizman, B Paul Morgan, Ora Schueler-Furman, Elior Peles, Dror Mevorach

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

14 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  9. Article
  10. Association of Blood Group Antigen CD59 with Disease.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2022
    Review
  11. Review
  12. Review
  13. A cryptic non-GPI-anchored cytosolic isoform of CD59 controls insulin exocytosis in pancreatic β-cells by interaction with SNARE proteins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  14. Evolution and Medical Significance of LU Domain-Containing Proteins.International journal of molecular sciences · 2019
    Review
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

8 authors at 2 institutions in 2 countries.

Netanel KarbianRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Yael Eshed-EisenbachRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Adi TabibRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Hila HoizmanRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
B Paul MorganRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Ora Schueler-FurmanRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Elior PelesRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Dror MevorachRheumatology Research Center (N.K., A.T., H.H., D.M.), Center of Rare Diseases, and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Weizmann Institute (Y.E.-E., E.P.), Rehovot, Israel; Systems Immunity Research Institute (B.P.M.), Cardiff University, Cardiff, Wales, UK; and Hebrew University (O.S.-F., D.M.), Jerusalem, Israel.
Cardiff University · GBWeizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo characterize all 4 mutations described for CD59 congenital deficiency.

methodsThe 4 mutations, p.Cys64Tyr, p.Asp24Val, p.Asp24Valfs*, and p.Ala16Alafs*, were described in 13 individuals with CD59 malfunction. All 13 presented with recurrent Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, recurrent strokes, and chronic hemolysis. Here, we track the molecular consequences of the 4 mutations and their effects on CD59 expression, localization, glycosylation, degradation, secretion, and function. Mutants were cloned and inserted into plasmids to analyze their expression, localization, and functionality.

resultsImmunolabeling of myc-tagged wild-type (WT) and mutant CD59 proteins revealed cell surface expression of p.Cys64Tyr and p.Asp24Val detected with the myc antibody, but no labeling by anti-CD59 antibodies. In contrast, frameshift mutants p.Asp24Valfs* and p.Ala16Alafs* were detected only intracellularly and did not reach the cell surface. Western blot analysis showed normal glycosylation but mutant-specific secretion patterns. All mutants significantly increased MAC-dependent cell lysis compared with WT. In contrast to CD59 knockout mice previously used to characterize phenotypic effects of CD59 perturbation, all 4 hCD59 mutations generate CD59 proteins that are expressed and may function intracellularly (4) or on the cell membrane (2). None of the 4 CD59 mutants are detected by known anti-CD59 antibodies, including the 2 variants present on the cell membrane. None of the 4 inhibits membrane attack complex (MAC) formation.

conclusionsAll 4 mutants generate nonfunctional CD59, 2 are expressed as cell surface proteins that may function in non-MAC-related interactions and 2 are expressed only intracellularly. Distinct secretion of soluble CD59 may have also a role in disease pathogenesis.

Identifiers

PMID30533526
PMCPMC6244018
OpenAlexW2898819798

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.