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Am J Transplant. 2017 Oct;17(10):2627-2639. doi: 10.1111/ajt.14283. Epub 2017 May 2.

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

Author information

1
Immune Tolerance Network, Massachusetts General Hospital, Bethesda, MD.
2
Departments of Medicine and Surgery, University of California, San Francisco, CA.
3
Northwestern Memorial Hospital, Northwestern University, Chicago, IL.
4
Beth Israel Deaconess Medical Center, Boston, MA.
5
Cleveland Clinic, Cleveland, OH.
6
Recanati Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
7
University of Alabama School of Medicine, Birmingham, AL.
8
Division of Allergy, Immunology, and Transplantation (DAIT), National Institute for Allergy and Infectious Diseases, Rockville, MD.
9
Department of Surgery, Emory University School of Medicine, Emory University, Atlanta, GA.
10
Bringham and Women's Hospital, Boston, MA.
11
Center for Transplantation Sciences and Immune Tolerance Network, Massachusetts General Hospital, Boston, MA.

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.

KEYWORDS:

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

PMID:
28371372
PMCID:
PMC5620117
DOI:
10.1111/ajt.14283
[Indexed for MEDLINE]
Free PMC Article

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