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Insights from computational modeling in inflammation and acute rejection in limb transplantation

Wolfram, D and Starzl, R and Hackl, H and Barclay, D and Hautz, T and Zelger, B and Brandacher, G and Lee, WPA and Eberhart, N and Vodovotz, Y and Pratschke, J and Pierer, G and Schneeberger, S (2014) Insights from computational modeling in inflammation and acute rejection in limb transplantation. PLoS ONE, 9 (6).

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Abstract

Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. © 2014 Wolfram et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wolfram, D
Starzl, R
Hackl, H
Barclay, Ddeb7@pitt.eduDEB7
Hautz, T
Zelger, B
Brandacher, G
Lee, WPA
Eberhart, N
Vodovotz, Yvodovotz@pitt.eduVODOVOTZ
Pratschke, J
Pierer, G
Schneeberger, S
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBueno, ValquiriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 13 June 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0099926
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
Date Deposited: 01 Jul 2014 16:11
Last Modified: 04 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/22109

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