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

• Type of Material: Article
• Authors: Kenneth Newell, Emory University; Andrew B. Adams, Emory University; Laurence A. Turka, Massachusetts General Hospital
• Language: English
• Date: 2018-05-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Society for Histocompatibility and Immunogenetics
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.humimm.2018.02.007
• Title of Journal or Parent Work: Human Immunology
• ISSN: 0198-8859
• Volume: 79
• Issue: 5
• Start Page: 380
• End Page: 387
• Grant/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.
• Keywords: Immunology; TACROLIMUS; SIGNATURE; MAINTENANCE IMMUNOSUPPRESSION; Tolerance; Kidney; Biomarkers; ALLOGRAFT TOLERANCE; HUMANS; EXPRESSION; MISMATCHED RENAL-TRANSPLANTATION; B cells; B-CELLS; Life Sciences & Biomedicine; Transplantation; IDENTIFICATION; Science & Technology; LIVER
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

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.