Evidence map›Paper›PMID 30092338›Full record

ArticleTransplant immunology2018

B cell phenotypes in baboons with pig artery patch grafts receiving conventional immunosuppressive therapy.

Takayuki Yamamoto, Qi Li, Hidetaka Hara, Liaoran Wang, Hongmin Zhou, Juan Li, Devin E Eckhoff, A Joseph Tector, Edwin C Klein, Ray Lovingood and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Transplant immunology, 2018. 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
1.4field-weighted citation impact, top 19% 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, 11 citations in OpenAlex.

  1. Review
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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

15 authors at 4 institutions in 2 countries.

Takayuki YamamotoXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Qi LiXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Second Affiliated Hospital, University of South China, Hengyang City, Hunan, China.
Hidetaka HaraXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Liaoran WangXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Second Affiliated Hospital, University of South China, Hengyang City, Hunan, China.
Hongmin ZhouXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Juan LiXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Second Affiliated Hospital, University of South China, Hengyang City, Hunan, China.
Devin E EckhoffXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
A Joseph TectorXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Edwin C KleinThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Ray LovingoodKirklin Clinic Pharmacy, University of Alabama at Birmingham, Birmingham, AL, USA.
Mohamed EzzelarabThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
David AyaresRevivicor, Blacksburg, VA, USA.
Yi WangSecond Affiliated Hospital, University of South China, Hengyang City, Hunan, China.
David K C CooperXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Hayato IwaseXenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: hiwase@uabmc.edu.
University of Alabama at Birmingham · USUniversity of Pittsburgh · USTongji University · CNUniversity of South China · CN

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

backgroundIn the pig-to-baboon artery patch model with no immunosuppressive therapy, a graft from an α1,3-galactosyltransferase gene-knockout (GTKO) pig elicits a significant anti-nonGal IgG response, indicating sensitization to the graft. A costimulation blockade-based regimen, e.g., anti-CD154mAb or anti-CD40mAb, prevents sensitization. However, neither of these agents is currently FDA-approved. The aim of the present study was to determine the efficacy of FDA-approved agents on the T and B cell responses.

methodsArtery patch xenotransplantation in baboons was carried out using GTKO/CD46 pigs with (n = 2) or without (n = 1) the mutant transgene for CIITA-knockdown. Immunosuppressive therapy consisted of induction with ATG and anti-CD20mAb, and maintenance with different combinations of CTLA4-Ig, tacrolimus, and rapamycin. In addition, all 3 baboons received daily corticosteroids, the IL-6R blocker, tocilizumab, at regular intervals, and the TNF-α blocker, etanercept, for the first 2 weeks. Recipient blood was monitored for anti-nonGal antibody levels by flow cytometry (using GTKO/CD46 pig aortic endothelial cells), and mixed lymphocyte reaction (MLR). CD22

resultsNo elicited anti-pig antibodies developed in any baboon. The frequency of naïve memory B cells increased significantly (from 34% to 90%, p = 0.0015), but there was a significant decrease in switched memory B cells (from 17% to 0.5%, p = 0.015). MLR showed no increase in the proliferative T cell response in those baboons that had received CTLA4-Ig (n = 2). Histological examination showed few or no features of rejection in any graft.

conclusionsThe data suggest that immunosuppressive therapy with only FDA-approved agents may be adequate to prevent an adaptive immune response to a genetically-engineered pig graft, particularly if CTLA4-Ig is included in the regimen, in part because the development of donor-specific memory B cells is inhibited.

Indexed as

AbataceptAdaptive ImmunityAnimalsArteriesB-LymphocytesCells, CulturedDrug ApprovalGalactosyltransferasesGene Knockout TechniquesGraft RejectionImmunosuppressive AgentsPapioPhenotypeSirolimusSwineTacrolimusAbataceptGalactosyltransferasesImmunosuppressive AgentsSirolimusTacrolimusUDP-galactose-lactosylceramide alpha 1-4-galactosyltransferaseArtery patchCTLA4-IgFDA-approved agentsPigRapamycinTacrolimusXenotransplantation

Identifiers

PMID30092338
PMCPMC6249078
OpenAlexW2885710033

What OpenQuestion holds

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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.