Evidence map›Paper›PMID 32442648›Full record

ArticleJournal of proteomics2020

Longitudinal proteomics analysis in the immediate microenvironment of islet allografts during progression of rejection.

Oscar Alcazar, Luis F Hernandez, Ernesto S Nakayasu, Paul D Piehowski, Charles Ansong, Midhat H Abdulreda, Peter Buchwald

Open access · greenAbstract read
In one paragraph

Article in Journal of proteomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 9 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

7 authors at 2 institutions in 1 country.

Oscar AlcazarUniversity of Miami Miller School of Medicine, Diabetes Research Institute, Miami, FL, USA.
Luis F HernandezUniversity of Miami Miller School of Medicine, Diabetes Research Institute, Miami, FL, USA.
Ernesto S NakayasuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Paul D PiehowskiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Charles AnsongBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Midhat H AbdulredaUniversity of Miami Miller School of Medicine, Diabetes Research Institute, Miami, FL, USA; University of Miami Miller School of Medicine, Department of Surgery, Miami, FL, USA; University of Miami Miller School of Medicine, Department of Microbiology and Immunology, Miami, FL, USA; University of Miami Miller School of Medicine, Department of Ophthalmology, Miami, FL, USA. Electronic address: mabdulreda@miami.edu.
Peter BuchwaldUniversity of Miami Miller School of Medicine, Diabetes Research Institute, Miami, FL, USA; University of Miami Miller School of Medicine, Department of Molecular and Cellular Pharmacology, Miami, FL, USA. Electronic address: pbuchwald@med.miami.edu.
University of Miami · USPacific Northwest National Laboratory · US

Funding

Aptamer chimeras for the in vivo modulation of beta cell mass and immunogenicityUC4DK116241 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ABDULREDA, MIDHAT H, SERAFINI, PAOLO · 2017 to 2017
$2.0M
Role of macrophages in pancreatic islet graft rejectionK01DK097194 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ABDULREDA, MIDHAT H · 2013 to 2015
$415k
Mechanisms of islet transplant immune toleranceR56AI130330 · NIAID · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ABDULREDA, MIDHAT H · 2017 to 2017
$384k
NIAID NIH HHS R56 AI130330NIDDK NIH HHS K01 DK097194NIDDK NIH HHS UC4 DK116241
6 · The paper itself

Abstract

The applicability and benefits of pancreatic islet transplantation are limited due to various issues including the need to avoid immune-mediated rejection. Here, we used our experimental platform of allogeneic islet transplant in the anterior chamber of the eye (ACE-platform) to longitudinally monitor the progress of rejection in mice and obtain aqueous humor samples representative of the microenvironment of the graft for accurately-timed proteomic analyses. LC-MS/MS-based proteomics performed on such mass-limited samples (~5 μL) identified a total of 1296 proteins. Various analyses revealed distinct protein patterns associated with the mounting of the inflammatory and immune responses and their evolution with the progression of the rejection. Pathway analyses indicated predominant changes in cytotoxic functions, cell movement, and innate and adaptive immune responses. Network prediction analyses revealed transition from humoral to cellular immune response and exacerbation of pro-inflammatory signaling. One of the proteins identified by this localized proteomics as a candidate biomarker of islet rejection, Cystatin 3, was further validated by ELISA in the aqueous humor. This study provides (1) experimental evidence demonstrating the feasibility of longitudinal localized proteomics using small aqueous humor samples and (2) proof-of-concept for the discovery of biomarkers of impending immune attack from the immediate local microenvironment of ACE-transplanted islets. SIGNIFICANCE: The combination of the ACE-platform and longitudinal localized proteomics offers a powerful approach to biomarker discovery during the various stages of immune reactions mounted against transplanted tissues including pancreatic islets. It also supports proteomics-assisted drug discovery and development efforts aimed at preventing rejection through efficacy assessment of new agents by noninvasive and longitudinal graft monitoring.

Indexed as

Islets of Langerhans TransplantationProteomicsAllograftsAnimalsChromatography, LiquidGraft RejectionMiceTandem Mass SpectrometryAllogeneic pancreatic isletsAllograft rejectionAllorejectionAnterior chamber of the eyeImmune biomarkersIntraocular islet transplantationIslet microenvironmentLocalized proteomicsType 1 diabetes (T1D)

Identifiers

PMID32442648
PMCPMC7483621
OpenAlexW3027622431

What OpenQuestion holds

Textmetadata
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.