Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance

BMC Nephrol. 2015 Aug 19;16:146. doi: 10.1186/s12882-015-0141-2.

Abstract

Background: Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects.

Methods: The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis.

Results: rATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group.

Conclusion: The rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antilymphocyte Serum / therapeutic use
  • Basiliximab
  • CD3 Complex / genetics
  • Calcineurin Inhibitors / therapeutic use
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression / drug effects*
  • Graft Rejection / genetics
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Granzymes / genetics
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / genetics
  • Immunosuppression / methods
  • Immunosuppressive Agents / therapeutic use
  • Induction Chemotherapy / methods*
  • Kidney Transplantation / methods*
  • Lymphocyte Count
  • Male
  • Mannosidases / genetics
  • Middle Aged
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / immunology
  • Perforin / genetics
  • Prospective Studies
  • RNA, Messenger / blood
  • Recombinant Fusion Proteins / therapeutic use
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antilymphocyte Serum
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Calcineurin Inhibitors
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents
  • PRF1 protein, human
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Perforin
  • Basiliximab
  • Mannosidases
  • mannosyl-oligosaccharide 1,2-alpha-mannosidase
  • GZMB protein, human
  • Granzymes