Evidence map›Paper›PMID 36330055›Full record

ArticleFrontiers in medicine2022

Phosphorylation of S6RP in peritubular capillaries of kidney grafts and circulating HLA donor-specific antibodies.

Dalia Raïch-Regué, Javier Gimeno, Laura Llinàs-Mallol, Silvia Menéndez, David Benito, Dolores Redondo, M José Pérez-Sáez, Marta Riera, Elaine F Reed, Julio Pascual and 1 more

Abstract read
In one paragraph

Article in Frontiers in medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2023
    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.

Dalia Raïch-ReguéHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Javier GimenoHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Laura Llinàs-MallolHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Silvia MenéndezHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
David BenitoHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Dolores RedondoHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
M José Pérez-SáezHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Marta RieraHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Elaine F ReedDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Julio PascualHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Marta CrespoHospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-mediated rejection (ABMR) caused by donor-specific HLA-antibodies (DSA) is a mediator of allograft loss after kidney transplantation (KT). DSA can activate microvascular endothelium damage through the mTOR pathway. In this study we assessed the mTOR pathway activation by DSA in KT with ABMR (ABMR + DSA+) compared to controls (ABMR-DSA-), biopsies with ABMR changes without DSA (ABMR + DSA-) and DSA without ABMR changes (ABMR-DSA+), and the potential modulation by mTOR inhibitors (mTORi). We evaluated 97 biopsies: 31 ABMR + DSA+, 33 controls ABMR-DSA-, 16 ABMR + DSA-, and 17 ABMR-DSA+ cases. Regarding immunosuppression of full ABMR + DSA+ and controls, 21 biopsies were performed under mTORi treatment (11 of them ABMR + DSA+ cases) and 43 without mTORi (20 of them ABMR + DSA+) so as to explore its effect on the mTOR pathway. Biopsies were stained for C4d, Ki67, and phosphorylated (p) S6RP, ERK, and mTOR by immunohistochemistry. Labeling was graded according to peritubular capillary staining. ABMR biopsies showed significantly higher C4d, p-S6RP, and Ki67 staining in peritubular capillaries (PTC) compared to controls, and light differences in p-ERK or p-mTOR. mTORi treatment did not modify p-S6RP, p-mTOR, and p-ERK staining. Diffuse p-S6RP in PTC in the biopsies significantly associated with circulating HLA-DSA independently of graft rejection, and with worse death-censored graft survival. These findings suggest that activation of endothelium through the mTOR pathway evidence different mechanisms of damage in ABMR + DSA+ and ABMR + DSA- despite similar histological injury.

Indexed as

antibody mediated allograft rejectiondonor specific antibodiesmammalian target of rapamycin (mTOR)peritubular capillariesphosphorylationribosomal protein S6 (S6RP)transplantation—kidney

Identifiers

PMID36330055
PMCPMC9622791

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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.