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      Immunologic monitoring in kidney transplant recipients

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          Abstract

          Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work-up of renal allograft dysfunction—an update. Curr Opin Nephrol Hypertens 8:723–728, 1999). A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the “drug level” era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients.

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          Regulatory T cells in transplantation tolerance.

          Shimon Sakaguchi, Robert Wood (2003)
          The identification and characterization of regulatory T (T(Reg)) cells that can control immune responsiveness to alloantigens have opened up exciting opportunities for new therapies in transplantation. After exposure to alloantigens in vivo, alloantigen-specific immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25. In vivo, common mechanisms seem to underpin the activity of CD4+CD25+ T(Reg) cells in both naive and manipulated hosts. However, the origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ T(Reg) cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate..
          Article 0 comments Cited 162 times – based on 0 reviews     Review now
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            Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans.

            Pervinder Sagoo, Esperanza Perucha, Birgit Sawitzki … (2010)
            Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.
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              Desensitization in HLA-incompatible kidney recipients and survival.

              Robert Montgomery, Bonnie Lonze, Karen E. King … (2011)
              More than 20,000 candidates for kidney transplantation in the United States are sensitized to HLA and may have a prolonged wait for a transplant, with a reduced transplantation rate and an increased rate of death. One solution is to perform live-donor renal transplantation after the depletion of donor-specific anti-HLA antibodies. Whether such antibody depletion results in a survival benefit as compared with waiting for an HLA-compatible kidney is unknown. We used a protocol that included plasmapheresis and the administration of low-dose intravenous immune globulin to desensitize 211 HLA-sensitized patients who subsequently underwent renal transplantation (treatment group). We compared rates of death between the group undergoing desensitization treatment and two carefully matched control groups of patients on a waiting list for kidney transplantation who continued to undergo dialysis (dialysis-only group) or who underwent either dialysis or HLA-compatible transplantation (dialysis-or-transplantation group). In the treatment group, Kaplan-Meier estimates of patient survival were 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and 30.5%, respectively, for patients in the dialysis-only group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons). Live-donor transplantation after desensitization provided a significant survival benefit for patients with HLA sensitization, as compared with waiting for a compatible organ. By 8 years, this survival advantage more than doubled. These data provide evidence that desensitization protocols may help overcome incompatibility barriers in live-donor renal transplantation. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Charles T. Bauer Foundation.).
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                Author and article information

                Contributors
                Anil Chandraker
                Journal
                Journal ID (nlm-ta): Kidney Res Clin Pract
                Journal ID (iso-abbrev): Kidney Res Clin Pract
                Title: Kidney Research and Clinical Practice
                Publisher: Elsevier
                ISSN (Print): 2211-9132
                ISSN (Electronic): 2211-9140
                Publication date PMC-release: 29 May 2013
                Publication date (Print): June 2013
                Publication date (Electronic): 29 May 2013
                Volume: 32
                Issue: 2
                Pages: 52-61
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
                [2 ]Schuster Family Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
                Author notes
                [* ]Corresponding author. Schuster Family Transplantation Research Center, Renal Division, Brighamand Women's Hospital, Harvard Medical School, 75 Francis street MRB-4, Boston, MA 02115, USA. achandraker@ 123456rics.bwh.harvard.edu
                Article
                Publisher ID: S2211-9132(13)00024-7
                DOI: 10.1016/j.krcp.2013.04.002
                PMC ID: 4713911
                PubMed ID: 26877913
                SO-VID: 7bccddec-7e54-4ba8-bc1d-f79de98c8f2f
                Copyright © © 2013. The Korean Society of Nephrology. Published by Elsevier.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 3 December 2012
                Date accepted : 10 January 2013
                Categories
                Subject: Review Article

                Keywords: immunology,kidney transplant,monitoring,recipient
                Data availability:
                Keywords: immunology, kidney transplant, monitoring, recipient

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