Evidence map›Paper›PMID 36227902›Full record

ArticlePloS one2022

APRIL/BLyS deficient rats prevent donor specific antibody (DSA) production and cell proliferation in rodent kidney transplant model.

Natalie M Bath, Bret M Verhoven, Nancy A Wilson, Weifeng Zeng, Weixiong Zhong, Lauren Coons, Arjang Djamali, Robert R Redfield

Abstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Natalie M BathDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.ORCID 0000-0002-7245-9000
Bret M VerhovenDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Nancy A WilsonDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.ORCID 0000-0002-9472-6026
Weifeng ZengDivision of Plastic Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Weixiong ZhongDepartment of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Lauren CoonsDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Arjang DjamaliDepartment of Medicine, Maine Medical Center, Portland, Maine, United States of America.
Robert R RedfieldDivision of Transplant, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Funding

Institutional Clinical and Translational Science AwardKL2TR000428 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$6.2M
NCATS NIH HHS KL2 TR000428
6 · The paper itself

Abstract

APRIL (A proliferation inducing ligand) and BLyS (B Lymphocyte Stimulator) are two critical survival factors for B lymphocytes and plasma cells, the main source of alloantibody. We sought to characterize the specific effects of these cytokines in a kidney transplant model of antibody mediated rejection (AMR). We engineered APRIL-/- and BLyS-/- Lewis rats using CRISPR/Cas9. APRIL-/- and BLyS-/- rats were sensitized with Brown Norway (BN) blood (complete MHC mismatch). Twenty-one days following sensitization, animals were harvested and collected tissues were analyzed using flow cytometry, ELISPOT, and immunohistochemistry. Flow cross match and a 3 day mixed lymphocyte reaction (MLR) was performed to assess donor specific antibody (DSA) production and T-cell proliferation, respectively. Sensitized dual knock out Lewis rats (APRIL-/-/BLyS-/-) underwent kidney transplantation and were sacrificed on day 7 post-transplant. Sensitized BLyS-/- had significant decreases in DSA and cell proliferation compared to WT and APRIL-/- (p<0.02). Additionally, BLyS-/- rats had a significant reduction in IgG secreting cells in splenic marginal zone B lymphocytes, and in cell proliferation when challenged with alloantigen compared to WT and APRIL-/-. Transplanted APRIL-/-/BLyS-/- rodents had significantly less DSA and antibody secreting cells compared to WT (p<0.05); however, this did not translate into a significant difference in AMR seen between groups. In summary, our studies suggest that APRIL and BLyS play a greater role in DSA generation rather than AMR, highlighting the role of cellular pathways that regulate AMR.

Indexed as

Kidney TransplantationAnimalsB-Cell Activating FactorCell ProliferationGraft RejectionImmunoglobulin GIsoantibodiesIsoantigensRatsRats, Inbred LewRodentiaTumor Necrosis Factor Ligand Superfamily Member 13B-Cell Activating FactorImmunoglobulin GIsoantibodiesIsoantigensTNFSF13 protein, humanTumor Necrosis Factor Ligand Superfamily Member 13

Identifiers

PMID36227902
PMCPMC9562156

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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.