Evidence map›Paper›PMID 35109826›Full record

ArticleBMC nephrology2022

Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation.

Angelica Canossi, Samuele Iesari, Quirino Lai, Simone Ciavatta, Tiziana Del Beato, Alessandra Panarese, Barbara Binda, Alessandra Tessitore, Franco Papola, Francesco Pisani

Open access · goldAbstract read
In one paragraph

Article in BMC nephrology, 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
0.8field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

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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 4 institutions in 2 countries.

Angelica CanossiCNR Institute for Translational Pharmacology, Via Giosuè Carducci 32C, 67100, L'Aquila, Italy. angelica.canossi@cnr.it.
Samuele IesariDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Quirino LaiHepatobiliary and Organ Transplantation Unit, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
Simone CiavattaRegional Center for Organ Transplantation (CRT), S. Salvatore Hospital, Via Lorenzo Natali 1, 67100, L'Aquila, Italy.
Tiziana Del BeatoCNR Institute for Translational Pharmacology, Via Giosuè Carducci 32C, 67100, L'Aquila, Italy.
Alessandra PanareseRegional Center for Organ Transplantation (CRT), S. Salvatore Hospital, Via Lorenzo Natali 1, 67100, L'Aquila, Italy.
Barbara BindaRegional Center for Organ Transplantation (CRT), S. Salvatore Hospital, Via Lorenzo Natali 1, 67100, L'Aquila, Italy.
Alessandra TessitoreDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Franco PapolaRegional Centre of Immunohematology and Tissue Typing, San Salvatore Hospital, Via Lorenzo Natali 1, 67100, L'Aquila, Italy.
Francesco PisaniDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
San Salvatore Hospital · ITUniversity of L'Aquila · ITIstituto di Farmacologia Traslazionale · ITSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcute T-cell mediated rejection (aTCMR) is still an issue in kidney transplantation, for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict acute rejection onset, de novo donor-specific antibodies (DSA) development and renal dysfunction 1 year after transplantation.

methodsWe profiled by using a relative quantification analysis (qRT-PCR) circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60 and 365 days, and when possible at the acute rejection) and compared also the results with 24 healthy controls.

resultsThe three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at 1 year in comparison with baseline, with very low levels at the time of aTCMR for FOXP3 (RQ = 0.445, IQR = 0.086-1.264, p = 0.040), maybe for the pro-apoptotic role of FOXP3 during inflammation. A multivariate Cox regression analysis evidenced a significant relation between aTCMR onset and thymoglobuline induction (HR = 6.749 p = 0.041), everolimus use (HR = 7.017, p = 0.007) and an increased risk from the solCTLA-4 expression at 15 days, mainly considering recipients treated with Mycophelolic acid (HR = 13.94 p = 0.038, 95%CI:1.157-167.87). Besides, solCTLA-4 also predisposed to graft dysfunction (eGFR< 60 mL/min/1.73m

conclusionsmRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of "precision medicine".

Indexed as

Kidney TransplantationAdultBiomarkersCTLA-4 AntigenFemaleForkhead Transcription FactorsGene ExpressionGraft RejectionHumansLongitudinal StudiesMaleMiddle AgedPostoperative ComplicationsPredictive Value of TestsRNA, MessengerT-Lymphocytes, RegulatoryBiomarkersCTLA-4 AntigenCTLA4 protein, humanForkhead Transcription FactorsFOXP3 protein, humanRNA, MessengerCellular acute rejectionCTLA-4DSA developmentFOXP3Graft dysfunctionKidney transplantationRT-PCR

Identifiers

PMID35109826
PMCPMC8809010
OpenAlexW4210621663

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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.