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Curr Transplant Rep. 2019 Mar;6(1):60-68. doi: 10.1007/s40472-019-0225-1. Epub 2019 Jan 14.

High Dimensional Renal Profiling: Towards a Better Understanding or Renal Transplant Immune Suppression.

Author information

1
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
2
Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
3
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH.
4
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

Abstract

PURPOSE OF REVIEW:

The goal of this review is to discuss new approaches to avoid CNI/CCS toxicities with a focus on new biologics and new methods to understand transplant rejection at the single-cell level.

RECENT FINDINGS:

Recently developed biologics hold significant promise as the next wave of therapeutics designed to promote CNI/CCS-free long-term allograft acceptance. Indeed, belatacept, soluble CTLA4-Ig, is largely devoid of CNI-like toxicities, although it is accompanied by an increased frequency of acute rejection. Besides belatacept, other biologics hold promise as CNI-free immune suppressive approaches. Finally, powerful new single cell approaches can enable characterization of cellular populations that drive rejection within the rejecting allograft.

SUMMARY:

We propose that the incorporated single cell profiling into studies investigating new biologics in transplantation, could be tailored to each patient, correlated with potential biomarkers in the blood and urine, and provide a platform where therapeutic targets can be rationally defined, mechanistically-based, and exploited.

KEYWORDS:

belatacept; calcineurin inhibitor; high dimension profiling; immunosuppression; kidney allograft rejection; mTOR inhibitor; single cell RNA sequencing; toxicity

PMID:
31595214
PMCID:
PMC6781878
[Available on 2020-03-01]
DOI:
10.1007/s40472-019-0225-1

Conflict of interest statement

Conflict of Interest David Hildeman reports grants from University of Cincinnati Center for Clinical & Translational Science & Training. Cyd Castro-Rojas, Steve Woodle and Rita Alloway declare no conflict of interest.

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