Evidence map›Paper›PMID 40259710›Full record

ArticleXenotransplantation

Desensitization With Proteasome Inhibition and Costimulation Blockade Modulates the Xenoreactive Humoral Response in Nonhuman Primate Xenotransplantation.

Brendan P Lovasik, Abraham J Matar, Jakob Habib, David A Faber, Cynthia P Breeden, Alton B Farris, A Joseph Tector, Andrew B Adams

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Brendan P LovasikDepartment of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA.
Abraham J MatarEmory Transplant Center, Emory University, Atlanta, Georgia, USA.
Jakob HabibEmory Transplant Center, Emory University, Atlanta, Georgia, USA.
David A FaberEmory Transplant Center, Emory University, Atlanta, Georgia, USA.
Cynthia P BreedenEmory Transplant Center, Emory University, Atlanta, Georgia, USA.
Alton B FarrisDepartment of Pathology, Emory University, Atlanta, Georgia, USA.
A Joseph TectorDepartment of Surgery, University of Miami, Miami, Florida, USA.
Andrew B AdamsEmory Transplant Center, Emory University, Atlanta, Georgia, USA.

Funding

Strategies to Optimize Pig-to-Primate Kidney Xenograft SurvivalU01AI126322 · NIAID · UNIVERSITY OF MINNESOTA · PI Andrew B Adams, A Joseph Tector · 2021 to 2026
$8.9M
Optimizing Strategies to Overcome Kidney Xenograft RejectionR01AI126322 · NIAID · UNIVERSITY OF MINNESOTA · PI ADAMS, ANDREW B · 2016 to 2020
$4.6M
NIAID NIH HHS R01 AI126322NIAID NIH HHS U01 AI126322NIAID of the National Institutes of Health 5R01AI126322
6 · The paper itself

Abstract

introduction"Delayed" antibody-mediated xenograft rejection is one of the most important obstacles to clinical application of pig organ xenografts. The aim of this study was to assess the impact of a structured desensitization regimen including proteasome inhibition and next-generation costimulation blockade on xenoreactive antibodies.

methodsRhesus macaques with moderate-high pre-treatment xenoreactive antibody titers (N = 2) were selected. Recipients received twice-weekly carfilzomib (20 mg/m

resultsThe desensitization regimen resulted in a >50% depletion of CD38+CD27+ bone marrow plasma cells; these changes were progressive over the duration of the desensitization treatment period. The desensitization strategy and plasma cell depletion resulted in a progressive reduction in anti-pig IgG antibodies. Following xenotransplantation, both desensitized recipients demonstrated superior graft survival to a highly xenoreactive recipient (MST 30 days vs. 6 days), but neither desensitized recipient experienced prolonged graft survival.

conclusionsA structured desensitization regimen including proteasome inhibition and costimulation blockade results in plasma cell depletion and resultant reduction in circulating xenoreactive anti-pig IgG antibodies, with a modest improvement in xenograft survival. This desensitization regimen has promise for pig-to-NHP xenotransplant models.

Indexed as

Desensitization, ImmunologicGraft RejectionHeterograftsImmunity, HumoralProteasome InhibitorsTransplantation, HeterologousAnimalsMacaca mulattaSwineProteasome Inhibitorsantibodyproteasome inhibitionxenotransplantation

Identifiers

PMID40259710
PMCPMC12012413

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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.