Recent advances in precision medicine for individualized immunosuppression

Curr Opin Organ Transplant. 2020 Aug;25(4):420-425. doi: 10.1097/MOT.0000000000000771.

Abstract

Purpose of review: The current tools to proactively guide and individualize immunosuppression in solid organ transplantation are limited. Despite continued improvements in posttransplant outcomes, the adverse effects of over-immunosuppression or under-immunosuppression are common. The present review is intended to highlight recent advances in individualized immunosuppression.

Recent findings: There has been a great focus on genomic information to predict drug dose requirements, specifically on single nucleotide polymorphisms of CYP3A5 and ABCB1. Furthermore, biomarker studies have developed ways to better predict clinical outcomes, such as graft rejection.

Summary: The integration of advanced computing tools, such as artificial neural networks and machine learning, with genome sequencing has led to intriguing findings on individual or group-specific dosing requirements. Rapid computing allows for processing of data and discovering otherwise undetected clinical patterns. Genetic polymorphisms of CYP3A5 and ABCB1 have yielded results to suggest varying dose requirements correlated with race and sex. Newly proposed biomarkers offer precise and noninvasive ways to monitor patient's status. Cell-free DNA quantitation is increasingly explored as an indicator of allograft injury and rejection, which can help avoid unneeded biopsies and more frequently monitor graft function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppression Therapy / trends
  • Immunosuppressive Agents / administration & dosage
  • Organ Transplantation / methods*
  • Organ Transplantation / trends
  • Polymorphism, Single Nucleotide
  • Precision Medicine / methods*
  • Precision Medicine / trends
  • Transplantation, Homologous

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A