Evidence map›Paper›PMID 25381426›Full record

ArticleJournal of the American Society of Nephrology : JASN2015

Endothelial cell antibodies associated with novel targets and increased rejection.

Annette M Jackson, Tara K Sigdel, Marianne Delville, Szu-Chuan Hsieh, Hong Dai, Serena Bagnasco, Robert A Montgomery, Minnie M Sarwal

Abstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
12.0field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 130 citations in OpenAlex.

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  12. Re-Evaluating the Transplant Glomerulopathy Lesion-Beyond Donor-Specific Antibodies.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review
  13. Angiotensin II Type-1 Receptor Antibody in Solid Organ Transplantation - Is It Time to Test?Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review
  14. Review
  15. Article
  16. Article
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  18. Article
  19. Alloimmune Risk Stratification for Kidney Transplant Rejection.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Annette M JacksonDepartments of Medicine, ajackson@jhmi.edu minnie.sarwal@ucsf.edu.
Tara K SigdelDepartment of Surgery, University of California, San Francisco, California; and.
Marianne DelvilleTransplantation Rénale Adulte, Hôpital Necker, Paris, France.
Szu-Chuan HsiehDepartment of Surgery, University of California, San Francisco, California; and.
Hong DaiDepartment of Surgery, University of California, San Francisco, California; and.
Serena BagnascoPathology, and.
Robert A MontgomerySurgery, Johns Hopkins University, Baltimore, Maryland;
Minnie M SarwalDepartment of Surgery, University of California, San Francisco, California; and ajackson@jhmi.edu minnie.sarwal@ucsf.edu.
University of California, San Francisco · USJohns Hopkins University · USHôpital Necker-Enfants Malades · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The initial contact point between a recipient's immune system and a transplanted graft is the vascular endothelium. Clinical studies suggest a pathogenic role for non-HLA antiendothelial cell antibodies (AECAs) in allograft rejection; however, evidence linking AECAs of known specificity to in vivo vascular injury is lacking. Here, we used high-density protein arrays to identify target antigens for AECAs isolated from the sera of recipients of kidney transplants experiencing antibody-mediated rejection in the absence of donor-specific HLA antibodies. Four antigenic targets expressed on endothelial cells were identified: endoglin, Fms-like tyrosine kinase-3 ligand, EGF-like repeats and discoidin I-like domains 3, and intercellular adhesion molecule 4; the first three have been implicated in endothelial cell activation and leukocyte extravasation. To validate these findings, ELISAs were constructed, and sera from an additional 150 renal recipients were tested. All four AECAs were detected in 24% of pretransplant sera, and they were associated with post-transplant donor-specific HLA antibodies, antibody-mediated rejection, and early transplant glomerulopathy. AECA stimulation of endothelial cell cultures increased adhesion molecule expression and production of inflammatory cytokines: regulated on activation, normal T cell expressed and secreted PDGF and RESISTIN. These correlations between in vitro experiments and in vivo histopathology suggest that AECAs activate the vascular endothelium, amplifying the alloimmune response and increasing microvascular damage. Given the growing number of transplant candidates, a better understanding of the antigenic targets, beyond HLA, and mechanisms of immune injury will be essential for improving long-term allograft survival.

Indexed as

Kidney TransplantationAdultAgedAntibodiesAntigensCells, CulturedEndothelial CellsEndothelium, VascularEnzyme-Linked Immunosorbent AssayFemaleGraft RejectionHLA AntigensHumansMaleMiddle AgedProtein Array AnalysisAntibodiesAntigensHLA Antigensacute allograft rejectionendothelial cellsimmunology and pathologykidney transplantation

Identifiers

PMID25381426
PMCPMC4413753
OpenAlexW2136639485

What OpenQuestion holds

Textmetadata
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.