Biomarkers of operational tolerance following kidney transplantation – The immune tolerance network studies of spontaneously tolerant kidney transplant recipients

Kenneth A. Newell, Andrew B. Adams, Laurence A. Turka

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Studies of kidney transplant recipients who have developed spontaneous and sustained tolerance have revealed an association with B cells. Unexpectedly tolerant individuals are characterized by increased numbers and frequencies of B cells in the blood and increased expression of genes associated with B cells in the blood and urine. Comparisons of the B cell repertoires of tolerant individuals and those receiving immunosuppression reveal that not only are the B cells more numerous but developmental differences result in a repertoire comprised of more naïve and transitional B cells in the tolerant cohort. B cells isolated from tolerant individuals also display functional differences compared to those from individuals receiving immunosuppression. Many of these differences may serve to suppress alloimmunity. Lastly a significant number of transplant recipients receiving standard immunosuppression display B cell-biased patterns of gene expression predictive of tolerance or a pro-tolerogenic state. Interestingly, this pattern is associated with improved renal allograft function. While recent studies have raised the concern that immunosuppressive drugs heavily influence B cell-based “signatures of tolerance”, a substantial body of work suggests that differences in B cells may be a useful tool for identifying tolerant kidney transplant recipients or guiding their immunosuppressive management.

Original languageEnglish (US)
Pages (from-to)380-387
Number of pages8
JournalHuman Immunology
Volume79
Issue number5
DOIs
StatePublished - May 2018
Externally publishedYes

Bibliographical note

Funding Information:
These research projects were supported by awards N01 AI15416 and UM1 AI-109565 from the National Institute of Allergy and Infectious Disease to the Immune Tolerance Network, an international clinical research consortium headquartered at the Benaroya Research Institute.

Publisher Copyright:
© 2018 American Society for Histocompatibility and Immunogenetics

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • B cells
  • Biomarkers
  • Kidney
  • Tolerance
  • Transplantation

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