Modelling and optimal control of immune response of renal transplant recipients

J Biol Dyn. 2012;6(2):539-67. doi: 10.1080/17513758.2012.655328. Epub 2012 Feb 1.

Abstract

We consider the increasingly important and highly complex immunological control problem: control of the dynamics of immunosuppression for organ transplant recipients. The goal in this problem is to maintain the delicate balance between over-suppression (where opportunistic latent viruses threaten the patient) and under-suppression (where rejection of the transplanted organ is probable). First, a mathematical model is formulated to describe the immune response to both viral infection and introduction of a donor kidney in a renal transplant recipient. Some numerical results are given to qualitatively validate and demonstrate that this initial model exhibits appropriate characteristics of primary infection and reactivation for immunosuppressed transplant recipients. In addition, we develop a computational framework for designing adaptive optimal treatment regimes with partial observations and low-frequency sampling, where the state estimates are obtained by solving a second deterministic optimal tracking problem. Numerical results are given to illustrate the feasibility of this method in obtaining optimal treatment regimes with a balance between under-suppression and over-suppression of the immune system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Humans
  • Immunity / drug effects
  • Immunity / immunology*
  • Immunosuppression Therapy
  • Immunosuppressive Agents / pharmacology
  • Infections / microbiology
  • Infections / virology
  • Kidney Transplantation / immunology*
  • Models, Immunological*
  • Transplantation Immunology* / drug effects
  • Virus Activation / drug effects

Substances

  • Immunosuppressive Agents