title: B Cell Receptor Genes Associated With Tolerance Identify a Cohort of Immunosuppressed Patients With Improved Renal Allograft Graft Function.
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.
authors.affiliation: Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
authors.forename: A
authors.initials: A
authors.lastname: Asare
authors.affiliation: Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
authors.forename: S
authors.initials: S
authors.lastname: Kanaparthi
authors.affiliation: Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
authors.forename: N
authors.initials: N
authors.lastname: Lim
authors.affiliation: Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
authors.forename: D
authors.initials: D
authors.lastname: Phippard
authors.affiliation: Departments of Medicine and Surgery, University of California, San Francisco, CA.
authors.forename: F
authors.initials: F
authors.lastname: Vincenti
authors.affiliation: Northwestern Memorial Hospital, Northwestern University, Chicago, IL.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-9344-9928
authors.initials: J
authors.lastname: Friedewald
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Pavlakis
authors.affiliation: Cleveland Clinic, Cleveland, OH.
authors.forename: E
authors.initials: E
authors.lastname: Poggio
authors.affiliation: Recanati Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: P
authors.initials: P
authors.lastname: Heeger
authors.affiliation: University of Alabama School of Medicine, Birmingham, AL.
authors.forename: R
authors.initials: R
authors.lastname: Mannon
authors.affiliation: Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
authors.forename: B E
authors.initials: BE
authors.lastname: Burrell
authors.affiliation: Division of Allergy, Immunology, and Transplantation (DAIT), National Institute for Allergy and Infectious Diseases, Rockville, MD.
authors.forename: Y
authors.initials: Y
authors.lastname: Morrison
authors.affiliation: Division of Allergy, Immunology, and Transplantation (DAIT), National Institute for Allergy and Infectious Diseases, Rockville, MD.
authors.forename: N
authors.initials: N
authors.lastname: Bridges
authors.affiliation: Department of Surgery, Emory University School of Medicine, Emory University, Atlanta, GA.
authors.forename: I
authors.initials: I
authors.lastname: Sanz
authors.affiliation: Bringham and Women's Hospital, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Chandraker
authors.affiliation: Department of Surgery, Emory University School of Medicine, Emory University, Atlanta, GA.
authors.forename: K A
authors.initials: KA
authors.lastname: Newell
authors.affiliation: Center for Transplantation Sciences and Immune Tolerance Network, Massachusetts General Hospital, Boston, MA.
authors.forename: L A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008875:Middle Aged; D011446:Prospective Studies; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*
chemical_list: D017931:DNA Primers; D007166:Immunosuppressive Agents; D011947:Receptors, Antigen, B-Cell
keywords: biomarker; clinical research/practice; graft survival; kidney transplantation/nephrology