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      Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation

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          Abstract

          Infectious complications remain a leading cause of morbidity and mortality after solid organ transplantation (SOT), and largely depend on the net state of immunosuppression achieved with current regimens. Cytomegalovirus (CMV) is a major opportunistic viral pathogen in this setting. The application of strategies of immunological monitoring in SOT recipients would allow tailoring of immunosuppression and prophylaxis practices according to the individual's actual risk of infection. Immune monitoring may be pathogen-specific or nonspecific. Nonspecific immune monitoring may rely on either the quantification of peripheral blood biomarkers that reflect the status of a given arm of the immune response (serum immunoglobulins and complement factors, lymphocyte sub-populations, soluble form of CD30), or on the functional assessment of T-cell responsiveness (release of intracellular adenosine triphosphate following a mitogenic stimulus). In addition, various methods are currently available for monitoring pathogen-specific responses, such as CMV-specific T-cell-mediated immune response, based on interferon-γ release assays, intracellular cytokine staining or main histocompatibility complex-tetramer technology. This review summarizes the clinical evidence to date supporting the use of these approaches to the post-transplant immune status, as well as their potential limitations. Intervention studies based on validated strategies for immune monitoring still need to be performed.

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          Most cited references123

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          Epstein-Barr virus infection.

          J I Cohen (2000)
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            BK polyomavirus in solid organ transplantation.

            The human BK polyomavirus (BKV) is the major cause of polyomavirus-associated nephropathy (PyVAN) putting 1-15% of kidney transplant patients at risk of premature allograft failure, but is less common in other solid organ transplants. Because effective antiviral therapies are lacking, screening kidney transplant patients for BKV replication in urine and blood has become the key recommendation to guide the reduction of immunosuppression in patients with BKV viremia. This intervention allows for expanding BKV-specific cellular immune responses, curtailing of BKV replication in the graft, and clearance of BKV viremia in 70-90% patients. Postintervention rejection episodes occur in 8-12%, most of which are corticosteroid responsive. Late diagnosis is faced with irreversible functional decline, poor treatment response, and graft loss. Adjunct therapies such as cidofovir, leflunomide and intravenous immunoglobulins have been used, but the benefit is not documented in trials. Retransplantation after PyVAN is largely successful, but requires close monitoring for recurrent BKV viremia. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
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              Cytomegalovirus in solid organ transplantation.

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                Author and article information

                Journal
                Clin Transl Immunology
                Clin Transl Immunology
                Clinical & Translational Immunology
                Nature Publishing Group
                2050-0068
                February 2014
                28 February 2014
                : 3
                : 2
                : e12
                Affiliations
                [1 ]Division of Transplant Infectious Diseases, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto , Toronto, Ontario, Canada
                Author notes
                [* ]Transplant Infectious Diseases, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto , 585 University Avenue, PMB-11-1236, Toronto, Ontario, Canada M5G 2N2. E-mail: atul.humar@ 123456uhn.ca
                Article
                cti20143
                10.1038/cti.2014.3
                4232060
                25505960
                4b5534ef-d7b9-4a98-8c64-babdb61e423c
                Copyright © 2014 Australasian Society for Immunology Inc.

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                : 26 December 2013
                : 28 January 2014
                : 28 January 2014
                Categories
                Review

                cell-mediated immunity,cytomegalovirus,immune-monitoring strategies,infection,prediction,solid organ transplantation

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