Evidence map›Paper›PMID 25658605›Full record

Trial reportPloS one2015

The local complement activation on vascular bed of patients with systemic sclerosis: a hypothesis-generating study.

Cinzia Scambi, Sara Ugolini, T Sakari Jokiranta, Lucia De Franceschi, Oscar Bortolami, Valentina La Verde, Patrizia Guarini, Paola Caramaschi, Viviana Ravagnani, Guido Martignoni and 6 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Complement activation in secondary thrombotic microangiopathies.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
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  11. Review
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  14. The role of adipokines in systemic sclerosis: a missing link?Archives of dermatological research · 2019
    Review
  15. Article
  16. Observational
  17. Article
  18. Article
  19. Innate Immunity in Systemic Sclerosis.Current rheumatology reports · 2017
    Review
  20. 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

16 authors at 2 institutions in 2 countries.

Cinzia ScambiDepartment of Medicine, University of Verona, Verona, Italy.
Sara UgoliniDepartment of Medicine, University of Verona, Verona, Italy.
T Sakari JokirantaDepartment of Bacteriology and Immunology, Haartman Institute and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
Lucia De FranceschiDepartment of Medicine, University of Verona, Verona, Italy.
Oscar BortolamiResearch Support Unit and Biostatistics, Verona University Hospital, Verona, Italy.
Valentina La VerdeDepartment of Medicine, University of Verona, Verona, Italy.
Patrizia GuariniDepartment of Medicine, University of Verona, Verona, Italy.
Paola CaramaschiDepartment of Medicine, University of Verona, Verona, Italy.
Viviana RavagnaniDepartment of Medicine, University of Verona, Verona, Italy.
Guido MartignoniDepartment of Pathology and Diagnostics, University of Verona, Verona, Italy.
Chiara ColatoDepartment of Pathology and Diagnostics, University of Verona, Verona, Italy.
Serena PedronDepartment of Pathology and Diagnostics, University of Verona, Verona, Italy.
Fabio BenedettiDepartment of Medicine, University of Verona, Verona, Italy.
Marco SorioDepartment of Medicine, University of Verona, Verona, Italy.
Fabio PoliDepartment of Medicine, University of Verona, Verona, Italy.
Domenico BiasiDepartment of Medicine, University of Verona, Verona, Italy.
University of Verona · ITUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe role of complement system in the pathogenesis of systemic sclerosis (SSc) has been debated during the last decade but an evident implication in this disease has never been found. We carried out an explorative study on SSc patients to evaluate the expression of soluble and local C5b-9 complement complex and its relation with a complement regulator, the Membrane Cofactor Protein (MCP, CD46) on skin vascular bed as target distinctive of SSc disease. We also analyzed two polymorphic variants in the complement activation gene cluster involving the MCP region.

methodsC5b-9 plasma levels of SSc patients and healthy subjects were analyzed by ELISA assay. Archival skin biopsies of SSc patients and controls were subjected to immunofluorescence analysis to detect C5b-9 and MCP on vascular endothelial cells. The expression of MCP was validated by immunoblot analysis with specific antibody. Polymorphic variants in the MCP gene promoter were tested by a quantitative PCR technique-based allelic discrimination method.

resultsEven though circulating levels of C5b-9 did not differ between SSc and controls, C5b-9 deposition was detected in skin biopsies of SSc patients but not in healthy subjects. MCP was significantly lower in skin vessels of SSc patients than in healthy controls and was associated with the over-expression of two polymorphic variants in the MCP gene promoter, which has been related to more aggressive phenotypes in other immune-mediated diseases.

conclusionsOur results firsty document the local complement activation with an abnormal expression of MCP in skin vessels of SSc patients, suggesting that a subset of SSc patients might be exposed to more severe organ complications and clinical evolution due to abnormal local complement activation.

Indexed as

Endothelial CellsGene Expression RegulationMembrane Cofactor ProteinPolymorphism, GeneticPromoter Regions, GeneticScleroderma, SystemicAgedComplement ActivationComplement Membrane Attack ComplexFemaleHumansMaleMiddle AgedSkinCD46 protein, humanComplement Membrane Attack ComplexMembrane Cofactor Protein

Identifiers

PMID25658605
PMCPMC4319765
OpenAlexW2028781819

What OpenQuestion holds

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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.