Immunological Monitoring as a Guide to the Management of Transplant Recipients

Thomas, Francis T.; Lee, H.M.; Lower, Richard R.; Thomas, Judith M.

doi:10.1016/s0039-6109(16)41784-6

Cited by 18 publications

(7 citation statements)

References 32 publications

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“…Measurement of the primary in vitro response to direct recognition of allogeneic molecules occurs in the mixed lymphocyte reaction (MLR), in which recipient T cells are tested for reactivity to donor cells. In an MLR, peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days; donor lymphocytes are inactivated, thereby allowing only the recipient lymphocytes to proliferate in response to foreign histocompatibility antigens (one-way MLR) ( Table 1 and Figure 1 ) [13]. This reaction was first described in the 1960s using 3Hthy incorporation as a read-out, and has been extensively used to study anti-donor T cell responses.…”

Section: T Cell Alloreactivitymentioning

confidence: 99%

Monitoring alloimmune response in kidney transplantation

Bestard

Cravedi

2016

J Nephrol

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Currently, immunosuppressive therapy in kidney transplant recipients is generally performed by protocols and adjusted according to functional or histological evaluation of the allograft and/or signs of drug toxicity or infection. As a result, a large fraction of patients are likely to receive too much or too little immunosuppression, exposing them to higher rates of infection, malignancy and drug toxicity, or increased risk of acute and chronic graft injury from rejection, respectively. Developing reliable biomarkers is crucial for individualizing therapy aimed at extending allograft survival. Emerging data indicate that many assays, likely used in panels rather than single assays, have potential to be diagnostic and predictive of short and also long-term outcome. While numerous cross-sectional studies have found associations between the results of these assays and the presence of clinically relevant post-transplantation outcomes, data from prospective studies are still scanty, thereby preventing widespread implementation in the clinic. Of note, some prospective, randomized, multicenter biomarker-driven studies are currently on-going aiming at confirming such preliminary data. These works as well as other future studies are highly warranted to test the hypothesis that tailoring immunosuppression on the basis of results offered by these biomarkers leads to better outcomes than current standard clinical practice.

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Section: T Cell Alloreactivitymentioning

confidence: 99%

Monitoring alloimmune response in kidney transplantation

Bestard

Cravedi

2016

J Nephrol

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“…Mixed Lymphocyte Reaction (MLR) proliferation assaysMLR assays is the principle of reference, common to all different in vitro tests, in which T-cells from transplant recipients are faced for several hours or days to donor antigen presenting cells (APCs) and direct allogeneic reactivity is quantified by different methods. Mixed lymphocyte cultures were initially used to identify HLA class II antigens and to measure the degree of histocompatibility(71). Originally, incorporation of 3H thymidine as a result of cellular division was assessed after coculture.…”

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confidence: 99%

Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients

Crespo

Bestard

2016

Clinical Biochemistry

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“…In the classical form of MLR, peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days; in the one-way MLR test, donor lymphocytes are inactivated, thereby allowing only the recipient lymphocytes to proliferate in response to foreign histocompatibility antigens [14]. Lymphocyte proliferation (measured by tritiated thymidine uptake) provides information on the alloreactivity level of the patient.…”

Section: Peripheral Lymphocytes: Alloreactivity As a Marker Of Patienmentioning

confidence: 99%

Noninvasive methods to assess the risk of kidney transplant rejection

Cravedi

Mannon

2009

Expert Review of Clinical Immunology

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In current clinical practice, immune reactivity of kidney transplant recipients is estimated by monitoring the levels of immunosuppressive drugs, and by functional and/or histological evaluation of the allograft. The availability of assays that could directly quantify the extent of the recipient's immune response towards the allograft would help clinicians to customize the prescription of immunosuppressive drugs to individual patients. Importantly, these assays might provide a more indepth understanding of the complex mechanisms of acute rejection, chronic injury, and tolerance in organ transplantation, allowing the design of new and potentially more effective strategies for the minimization of immunosuppression, or even for the induction of immunological tolerance. The purpose of this review is to summarize results from recent studies in this field. Keywordsbiomarker; CD30; Cylex ™ ; ELISPOT; immune monitoring; proteomic; transplantation Transplant recipients, by and large, require immunosuppression indefinitely for the lifespan of their graft to prevent rejection; long-term maintenance of immunosuppression becomes a balance between suppressing rejection against the allograft and the toxicities associated with therapy, such as infections and malignancy. Acute clinical rejection still represents one of the major risk factors for poor long-term graft outcome [1] and, in kidney transplantation, the diagnosis of acute rejection is confirmed by renal allograft biopsy, which carries a finite risk of complications [2]. In clinical practice, a biopsy is commonly undertaken if there is a rise in serum creatinine of at least 15% above baseline, although this approach may fail to detect injury at its inception [3]. Indeed, serum creatinine is a relatively insensitive marker of renal dysfunction, which increases only in the late phases of injury when there has already been substantial functional loss. Moreover, in the absence of any changes in serum creatinine, up to one-third of renal allografts will demonstrate histological signs of acute rejection in the first 3 months after transplant [4]. These so-called 'subclinical rejections', if not detected and properly treated, may negatively affect long-term graft outcomes [5]. Protocol allograft biopsies may †Author

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Immunological Monitoring as a Guide to the Management of Transplant Recipients

Cited by 18 publications

References 32 publications

Monitoring alloimmune response in kidney transplantation

Monitoring alloimmune response in kidney transplantation

Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients

Noninvasive methods to assess the risk of kidney transplant rejection

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