Evidence map›Paper›PMID 30830041›Full record

ArticleTransplantation2019

APRIL/BLyS Blockade Reduces Donor-specific Antibodies in Allosensitized Mice.

Nancy A Wilson, Natalie M Bath, Bret M Verhoven, Xiang Ding, Brittney A Boldt, Adarsh Sukhwal, Weixiong Zhong, Sarah E Panzer, Robert R Redfield

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.5field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. 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

9 authors at 2 institutions in 1 country.

Nancy A WilsonDivision of Nephrology, Department of Medicine, University of Wisconsin-Madison, Madison, WI.
Natalie M BathDivision of Transplant, Department of Surgery, University of Wisconsin-Madison, Madison, WI.
Bret M VerhovenDivision of Transplant, Department of Surgery, University of Wisconsin-Madison, Madison, WI.
Xiang DingDepartment of Organ Transplantation, Xiangya Hospital, Central South University, Changsha, China.
Brittney A BoldtDivision of Transplant, Department of Surgery, University of Wisconsin-Madison, Madison, WI.
Adarsh SukhwalDepartment of Organ Transplantation, Xiangya Hospital, Central South University, Changsha, China.
Weixiong ZhongDepartment of Pathology, University of Wisconsin-Madison, Madison, WI.
Sarah E PanzerDivision of Nephrology, Department of Medicine, University of Wisconsin-Madison, Madison, WI.
Robert R RedfieldDivision of Transplant, Department of Surgery, University of Wisconsin-Madison, Madison, WI.
Central South University · CNXiangya Hospital Central South University · CN

Funding

Institutional Career Development CoreKL2TR002374 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI Bo Liu, Marin Leigh Schweizer · 2017 to 2026
$9.7M
Institutional Clinical and Translational Science AwardKL2TR000428 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$6.2M
University of Wisconsin Transplant Reseach Training ProgramT32AI125231 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KAUFMAN, DIXON B · 2016 to 2020
$1.2M
Improving long-term allograft survival in kidney transplantation by targeting B cell survival cytokinesK23DK122136 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI PANZER, SARAH E · 2019 to 2022
$663k
Special BD LSR FortessaS10OD018202 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI PATANKAR, MANISH S · 2014 to 2014
$351k
NCATS NIH HHS KL2 TR000428NCATS NIH HHS KL2 TR002374NIAID NIH HHS T32 AI125231NIDDK NIH HHS K23 DK122136NIH HHS S10 OD018202
6 · The paper itself

Abstract

backgroundHighly sensitized candidates on the transplant waitlist remain a significant challenge, as current desensitization protocols have variable success rates of donor-specific antibody (DSA) reduction. Therefore, improved therapies are needed. A proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS) are critical survival factors for B-lymphocytes and plasma cells, which are the primary sources of alloantibody production. We examined the effect of APRIL/BLyS blockade on DSA in a murine kidney transplant model as a possible novel desensitization strategy.

methodsC57BL/6 mice were sensitized with intraperitoneal (IP) injections of 2 × 10 BALB/c splenocytes. Twenty-one days following sensitization, animals were treated with 100 μg of BLyS blockade (B-cell activating factor receptor-immunoglobulin) or APRIL/BLyS blockade (transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin), administered thrice weekly for an additional 21 days. Animals were then euthanized or randomized to kidney transplant with Control Ig, BLyS blockade, or APRIL/BLyS blockade. Animals were euthanized 7 days posttransplant. B-lymphocytes and DSA of BLyS blockade only or APRIL/BLyS blockade-treated mice were assessed by flow cytometry, immunohistochemistry, and enzyme-linked immunospot.

resultsAPRIL/BLyS inhibition resulted in a significant reduction of DSA by flow crossmatch compared with controls (P < 0.01). APRIL/BLyS blockade also significantly depleted IgM- and IgG-secreting cells and B-lymphocyte populations compared to controls (P < 0.0001). APRIL/BLyS blockade in transplanted mice also resulted in decreased B-lymphocyte populations; however, no difference in rejection rates were seen between groups.

conclusionsAPRIL/BLyS blockade with transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin significantly depleted B-lymphocytes and reduced DSA in this sensitized murine model. APRIL/BLyS inhibition may be a clinically useful desensitization strategy for sensitized transplant candidates.

Indexed as

Desensitization, ImmunologicAnimalsB-Cell Activating FactorB-LymphocytesGraft RejectionGraft SurvivalImmunoglobulinsIsoantibodiesIsoantigensKidney TransplantationMice, Inbred BALB CMice, Inbred C57BLSpleenTime FactorsT-Lymphocyte SubsetsTumor Necrosis Factor Ligand Superfamily Member 13B-Cell Activating FactorImmunoglobulinsIsoantibodiesIsoantigensTnfsf13b protein, mouseTnfsf13 protein, mouseTumor Necrosis Factor Ligand Superfamily Member 13

Identifiers

PMID30830041
PMCPMC6594891
OpenAlexW2921857033

What OpenQuestion holds

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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.