High-Dimensional Renal Profiling: Towards a Better Understanding of Renal Transplant Immune Suppression

AbstractPurpose of ReviewThe goal of this review is to discuss new approaches to avoid calcineurin inhibitor (CNI)/corticosteroids (CCS) toxicities with a focus on new biologics and new methods to understand transplant rejection at the single-cell level.Recent FindingsRecently developed biologics hold significant promise as the next wave of therapeutics designed to promote CNI/CCS-free long-term allograft acceptance. Indeed, belatacept, soluble CTLA4-Ig, is largely devoid of CNI-like toxicities, although it is accompanied by an increased frequency of acute rejection. Besides belatacept, other biologics hold promise as CNI-free immune suppressive approaches. Finally, powerful new single-cell approaches can enable characterization of cellular populations that drive rejection within the rejecting allograft.SummaryWe propose that the incorporated single-cell profiling into studies investigating new biologics in transplantation could be tailored to each patient, correlated with potential biomarkers in the blood and urine, and provide a platform where therapeutic targets can be rationally defined, mechanistically based, and exploited.
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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SummaryImmunosuppression (IS) is administered to kidney transplant recipients to prevent rejection episodes and loss of the renal allograft. Most centers rely on a triple IS after induction with either interleukin ‑2 receptor antibodies or antithymocyte globulin. The most frequently used substances for maintenance IS are glucocorticoids, antimetabolites, mTOR inhibitors (mTORi), calcineurin inhibitors (CNI) and the costimulation blocker belatacept. Guidelines recommend a triple combination consisting of CNI s, antimetabolites and corticosteroids for the majority of patients. The long-term risk for malignancy in general i...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
We describe a case of MCD sixteen months post-transplant that has initially responded well to corticosteroid therapy.
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
Tabea Haug1, Michael Aigner1, Moritz M. Peuser1, Carolin D. Strobl1, Kai Hildner2, Dimitrios Mougiakakos1, Heiko Bruns1, Andreas Mackensen1 and Simon Völkl1* 1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany 2Department of Internal Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation m...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers. Introduction Despite great advances in immunosuppressive (IS) therapy, T cell-mediated rejection (TCMAR), which is the...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Noymar Luque-Campos1, Rafael A. Contreras-López1, María Jose Paredes-Martínez1, Maria Jose Torres2, Sarah Bahraoui3, Mingxing Wei4, Francisco Espinoza5, Farida Djouad3*, Roberto Javier Elizondo-Vega6* and Patricia Luz-Crawford1* 1Laboratorio de Inmunología Celular y Molecular, Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile 2Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile 3IRMB, INSERM, Univ Montpellier, Montpellier, France 4Cellvax, SAS...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, our findings identify ALCAM as a novel therapeutic target for preventing corneal allograft rejection in high-risk patient populations. Moreover, given the documented contribution of ALCAM to (lymph)angiogenesis, DC migration, and T cell activation, ALCAM blockade might represent a therapeutic strategy for treating other immune-mediated inflammatory conditions, such as solid organ transplant rejection, allergy or autoimmune diseases. Experimental Procedures Cloning, Expression, and Purification of I/F8-Fc and KSF-Fc For cloning of I/F8-Fc and KSF-Fc the respective scFv sequence was amplified from previousl...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: IL-2 receptor expression demonstrated the highest diagnostic accuracy, while the peripheral eosinophil count was the only marker tested in more than one study. Presently, liver biopsy remains superior to noninvasive diagnostic biomarkers as most studies exhibited inferior designs, hindering possible translation into clinical application. Introduction Liver transplantation (LT) exhibits 20-year survival rates of up to 50% (1) and is of great clinical importance. LT is the treatment of choice for acute or acute-on-chronic liver failure, while organ replacement therapies are still waiting for the break (2)...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Approximately 30% of patients undergoing heart transplantation (HTx) may have diabetes mellitus type 2 (DM2). More importantly, DM2 may become more prevalent after HTx because of high corticosteroid use. Metformin - an oral anti-hypoglycemic drug for DM2- has also been demonstrated to have immunomodulatory effects. It has been reported that metformin may decrease acute and chronic rejection as well as the development of cardiac allograft vasculopathy (CAV). Therefore, we reviewed our HTx patients placed on metformin pre-HTx and post-HTx to assess potential outcomes and benefits.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 678 Source Type: research
Conclusions The augmentation of conventional MMF plus corticosteroids with a CXCR4 antagonist is potentially effective in improving outcomes after heart transplantation in minipigs. Future studies are warranted into optimizing the therapeutic regimens for humans.
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science—General Source Type: research
Conclusion:A stable function was observed in all transplant recipients receiving the MIC cells product without any allograft injury or rejection episodes even under reduction of conventional therapy with immunosuppressive drugs. MIC cells constitute a novel tool for immunotherapy with a high potential in transplantation medicine.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 703. Adoptive Immunotherapy: Poster III Source Type: research
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