Evidence map›Paper›PMID 25511749›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2015

Phosphorylated S6 kinase and S6 ribosomal protein are diagnostic markers of antibody-mediated rejection in heart allografts.

Fang Li, Jennifer Wei, Nicole M Valenzuela, Chi Lai, Qiuheng Zhang, David Gjertson, Michael C Fishbein, Jon A Kobashigawa, Mario Deng, Elaine F Reed

Open access · greenAbstract read
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. International Society for Heart and Lung Transplantation Scientific Statement on pulmonary antibody-mediated rejection and proposed graft, antibody, and pathology (GAP) definition.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Guideline
  2. Trial
  3. The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020
    Review
  9. HLA and lung transplantation.Frontiers of medicine · 2019
    Review
  10. Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial cell-monocyte interactions via mTOR in transplant antibody-mediated rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018
    Article
  11. Review
  12. Review
  13. The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017
    Article
  14. Innate immune mechanisms in transplant allograft vasculopathy.Current opinion in organ transplantation · 2016
    Review
  15. Review
  16. 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

10 authors at 3 institutions in 1 country.

Fang Li *Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Jennifer Wei *Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Nicole M ValenzuelaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Chi LaiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Qiuheng ZhangDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
David GjertsonDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Michael C FishbeinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Jon A KobashigawaHeart Transplant Program, Cedars-Sinai Heart Institute, 127 S. San Vicente Blvd, Third Floor Cardiology A3107, los Angeles, CA 90048.
Mario DengUCLA Cardiovascular Center, Ronald Reagan UCLA Medical Center, UCLA Medical Center, Los Angeles, CA 90095, USA.
Elaine F ReedDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
University of California, Los Angeles · USCedars-Sinai Smidt Heart Institute · USRonald Reagan UCLA Medical Center · US

Funding

Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
Anti-MHC Effects on EndotheliumR01AI042819 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F · 1999 to 2014
$4.0M
Anti-HLA Antibody Activation of Endothelial Cells in Cardiac TransplantationR01HL090995 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F · 2008 to 2010
$1.2M
Anti-MHC Effects on EndotheliumR56AI042819 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F · 2015 to 2015
$385k
NHLBI NIH HHS 5T32HL069766-12NHLBI NIH HHS R01 HL090995NHLBI NIH HHS R01HL090995NHLBI NIH HHS T32 HL069766NIAID NIH HHS R01 AI042819NIAID NIH HHS R01AI042819NIAID NIH HHS R56 AI042819
6 · The paper itself

Abstract

backgroundAnti-MHC Class I alloantibodies have been implicated in the processes of acute and chronic rejection. These antibodies (Ab) bind to endothelial cells (EC) and transduce signals leading to the activation of cell survival and proliferation pathways, including Src, FAK and mTOR, as well as downstream targets ERK, S6 kinase (S6K) and S6 ribosomal protein (S6RP). We tested the hypothesis that phosphorylation of S6K, S6RP and ERK in capillary endothelium may serve as an adjunct diagnostic tool for antibody-mediated rejection (AMR) in heart allografts.

methodsDiagnosis of AMR was based on histology or immunoperoxidase staining of paraffin-embedded tissue, consistent with 2013 ISHLT criteria. Diagnosis of acute cellular rejection (ACR) was based on ISHLT criteria. Endomyocardial biopsies from 67 heart transplant recipients diagnosed with acute rejection [33 with pAMR, 18 with ACR (15 with Grade 1R, 3 with Grade ≥2R), 16 with pAMR and ACR (13 with 1R and 3 with ≥2R)] and 40 age- and gender-matched recipients without rejection were tested for the presence of phosphorylated forms of ERK, S6RP and S6K by immunohistochemistry.

resultsImmunostaining of endomyocardial biopsies with evidence of pAMR showed a significant increase in expression of p-S6K and p-S6RP in capillary EC compared with controls. A weaker association was observed between pAMR and p-ERK.

conclusionsBiopsies diagnosed with pAMR often showed phosphorylation of S6K and S6RP, indicating that staining for p-S6K and p-S6RP is useful for the diagnosis of AMR. Our findings support a role for antibody-mediated HLA signaling in the process of graft injury.

Indexed as

Heart TransplantationAdultAntibodiesBiomarkersFemaleGraft RejectionHumansMalePhosphorylationRibosomal Protein S6Ribosomal Protein S6 KinasesAntibodiesBiomarkersRibosomal Protein S6Ribosomal Protein S6 Kinasesantibody-mediated rejectionC4dcardiac allograftendomyocardial biopsyS6 kinase

Identifiers

PMID25511749
PMCPMC4402106
OpenAlexW2030540301

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.