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

• Type of Material: Article
• Authors: Adam Asare, Massachusetts General Hospital; Sai Kanaparthi, Massachusetts General Hospital; Noha Lim, Massachusetts General Hospital; Deborah Phippard, Massachusetts General Hospital; Flavio Vincenti, University of California San Francisco; John Friedewald, Northwestern University; Martha Pavlakis, Beth Israel Deaconess Medical Center; Emilio Poggio, Cleveland Clinic; Peter Heeger, Icahn School of Medicine at Mt Sinai; Roslyn Mannon, University of Alabama Birmingham; Bryna E. Burrell, Massachusetts General Hospital; Yvonne Morrison, National Institute of Allergy and Infectious Diseases; Nancy Bridges, National Institute of Allergy and Infectious Diseases; Ignacio Sanz, Emory University; Anil Chandraker, Bringham & Womens Hosp; Kenneth Newell, Emory University; Laurence A. Turka, Massachusetts General Hospital
• Language: English
• Date: 2017-10-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.14283
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 17
• Issue: 10
• Start Page: 2627
• End Page: 2639
• Grant/Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers U01 AI063594 (to Peter Heeger) and U01-AI063623 (to Anil Chandraker), NIH N01 AI15416 and UM1AI109565 (to the Immune Tolerance Network).
• Keywords: BIOMARKER; LIVING DONOR KIDNEY; Transplantation; CHIMERISM; KIDNEY-TRANSPLANT RECIPIENTS; PERIPHERAL-BLOOD; Science & Technology; PROFILE; Surgery; WITHDRAWAL; SIGNATURE; Life Sciences & Biomedicine; REJECTION; IDENTIFICATION
• Research Categories: Health Sciences, Medicine and Surgery

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.