B Cell Receptor Genes Associated With Tolerance Identify a Cohort of Immunosuppressed Patients With Improved Renal Allograft Graft Function

A. Asare, S. Kanaparthi, N. Lim, D. Phippard, F. Vincenti, J. Friedewald, M. Pavlakis, E. Poggio, P. Heeger, R. Mannon, B. E. Burrell, Y. Morrison, N. Bridges, I. Sanz, A. Chandraker, K. A. Newell, L. A. Turka, Jennifer Czerr, Karen Keslar, Maryanna LanningRita Spirko, Rivka Elbein, Terri Eubanks, Shine Thomas, Dasia Webster, Sarah Conte, Christine Dyer-Ward, Sudipta Tripathi, Jytte Birnbaum, Emmeline Chuu, Jennifer Cutler, Clarina Mendoza, Meghan Ford, Stephanie Laurer, Meghan Neil, Julia Ringel, Christin Rogers, Susan Brietigam, Jane Charette, Anna Zago, Brandy Haydel, Sherif Mikhail, Dominick Morrone, Denise Peace, Bernd Schroppel, Tina Ayer, Tena Hailey, Vineeta Kumar, Bridget Tate, Michele DesMarais, Winnie Felix, Peter Sayre, Nadia Tchao, David Ikle, Ann Nguyen, Dynel Oxendine, Katharine Spain, Theresa Allio

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We previously reported that two B cell receptor genes, IGKV1D-13 and IGKV4-1, were associated with tolerance following kidney transplantation. To assess the potential utility of this “signature,” we conducted a prospective, multicenter study to determine the frequency of patients predicted tolerant within a cohort of patients deemed to be candidates for immunosuppressive minimization. At any single time point, 25–30% of patients were predicted to be tolerant, while 13.7% consistently displayed the tolerance “signature” over the 2-year study. We also examined the relationship of the presence of the tolerance “signature” on drug use and graft function. Contrary to expectations, the frequency of predicted tolerance was increased in patients receiving tacrolimus and reduced in those receiving corticosteroids, mycophenolate mofetil, or Thymoglobulin as induction. Surprisingly, patients consistently predicted to be tolerant displayed a statistically and clinically significant improvement in estimated glomerular filtration rate that increased over time following transplantation. These findings indicate that the frequency of patients consistently predicted to be tolerant is sufficiently high to be clinically relevant and confirm recent findings by others that immunosuppressive agents impact putative biomarkers of tolerance. The association of a B cell–based “signature” with graft function suggests that B cells may contribute to the function/survival of transplanted kidneys.

Original languageEnglish (US)
Pages (from-to)2627-2639
Number of pages13
JournalAmerican Journal of Transplantation
Volume17
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • biomarker
  • clinical research/practice
  • graft survival
  • kidney transplantation/nephrology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Asare, A., Kanaparthi, S., Lim, N., Phippard, D., Vincenti, F., Friedewald, J., Pavlakis, M., Poggio, E., Heeger, P., Mannon, R., Burrell, B. E., Morrison, Y., Bridges, N., Sanz, I., Chandraker, A., Newell, K. A., Turka, L. A., Czerr, J., Keslar, K., ... Allio, T. (2017). B Cell Receptor Genes Associated With Tolerance Identify a Cohort of Immunosuppressed Patients With Improved Renal Allograft Graft Function. American Journal of Transplantation, 17(10), 2627-2639. https://doi.org/10.1111/ajt.14283