Evidence map›Paper›PMID 27159521›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2016

Enrichment of Scleroderma Vascular Disease-Associated Autoantigens in Endothelial Lineage Cells.

Zsuzsanna H McMahan, Tricia R Cottrell, Fredrick M Wigley, Brendan Antiochos, Elias T Zambidis, Tea Soon Park, Marc K Halushka, Laura Gutierrez-Alamillo, Raffaello Cimbro, Antony Rosen and 1 more

Open access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. T cells in SSc skin lesions: knowing your enemy.Nature reviews. Rheumatology · 2020
    Article
  6. 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

11 authors at 2 institutions in 1 country.

Zsuzsanna H McMahanJohns Hopkins University School of Medicine, Baltimore, Maryland.
Tricia R CottrellJohns Hopkins University School of Medicine, Baltimore, Maryland.
Fredrick M WigleyJohns Hopkins University School of Medicine, Baltimore, Maryland.
Brendan AntiochosJohns Hopkins University School of Medicine, Baltimore, Maryland.
Elias T ZambidisJohns Hopkins University School of Medicine, Baltimore, Maryland.
Tea Soon ParkJohns Hopkins University School of Medicine, Baltimore, Maryland.
Marc K HalushkaJohns Hopkins University School of Medicine, Baltimore, Maryland.
Laura Gutierrez-AlamilloJohns Hopkins University School of Medicine, Baltimore, Maryland.
Raffaello CimbroJohns Hopkins University School of Medicine, Baltimore, Maryland.
Antony RosenJohns Hopkins University School of Medicine, Baltimore, Maryland.
Livia Casciola-RosenJohns Hopkins University School of Medicine, Baltimore, Maryland. lcr@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Basic and Translational Research of iPSC-Based hematologic and Vascular TherapiesU01HL099775 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D · 2009 to 2015
$8.4M
Phenotype-Specific Immune Responses in the Systemic VasculitidesP30AR053503 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI ROSEN, ANTONY · 2006 to 2015
$6.4M
Mechanisms in Sjogrens SyndromeR01DE012354 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI ROSEN, ANTONY · 1998 to 2017
$3.4M
Pluripotent Stem Cell Vascular Therapies for Ischemic RetinopathiesR01EY023962 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2014 to 2018
$1.8M
Functional Vascular Progenitors from Naive Human iPSCR01HD082098 · NICHD · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2015 to 2019
$1.7M
Interferons and cytotoxic lymphocytes in dermatomyositis and cutaneous lupusR56AR062615 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CASCIOLA-ROSEN, LIVIA A, FIORENTINO, DAVID FRANKLIN · 2013 to 2013
$200k
NEI NIH HHS R01 EY023962NHLBI NIH HHS U01 HL099775NIAMS NIH HHS P30 AR053503NIAMS NIH HHS R56 AR062615NICHD NIH HHS R01 HD082098NIDCR NIH HHS R01 DE012354
6 · The paper itself

Abstract

objectiveScleroderma patients with autoantibodies to CENPs and/or interferon-inducible protein 16 (IFI-16) are at increased risk of severe vascular complications. This study was undertaken to determine whether these autoantigens are enriched in cells of the vasculature.

methodsSuccessive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI-16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI-16 and CD31 expression were defined in paraffin-embedded skin sections from scleroderma patients and from healthy controls. IFI-16 expression was determined by flow cytometric analysis in circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells.

resultsExpression of CENP-A, IFI-16, and CD31 was enriched in EBs on days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI-16, CD31, and CENPs A and B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of paraffin-embedded skin sections showed enrichment of IFI-16 in CD31-positive vascular endothelial cells in biopsy specimens from scleroderma patients and normal controls. Flow cytometric analysis revealed IFI-16 expression in circulating hematopoietic progenitor cells but minimal expression in CECs.

conclusionOur findings indicate that expression of the scleroderma autoantigens IFI-16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.

Indexed as

AutoantigensCase-Control StudiesCell LineageCentromere Protein ACentromere Protein BChromosomal Proteins, Non-HistoneEmbryoid BodiesEndothelial CellsEndothelial Progenitor CellsFlow CytometryHematopoietic Stem CellsHumansImmunoblottingImmunohistochemistryLeukocytes, MononuclearNuclear ProteinsAutoantigensCENPA protein, humanCENPB protein, humanCentromere Protein ACentromere Protein BChromosomal Proteins, Non-HistoneIFI16 protein, humanNuclear ProteinsPhosphoproteinsPlatelet Endothelial Cell Adhesion Molecule-1

Identifiers

PMID27159521
PMCPMC5042822
OpenAlexW2528828955

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.