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The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy

Immunosuppressive drugs are widely used to treat several autoimmune disorders and prevent rejection after organ transplantation. However, intra-individual variations in the pharmacological response to immunosuppressive therapy critically influence its efficacy, often resulting in poor treatment resp...

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Autores principales: Portoles, Jose Maria, Jimenez, Carlos, Janeiro, Dario, Lopez-Oliva, Maria O., Ortega-Carrion, Alvaro, Blanquez, Daniel, Arribas, Luis, Gomez, Carlos, Diez, Teresa, Pascual, Julio, Portero, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868528/
https://www.ncbi.nlm.nih.gov/pubmed/33569062
http://dx.doi.org/10.3389/fimmu.2020.618202
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author Portoles, Jose Maria
Jimenez, Carlos
Janeiro, Dario
Lopez-Oliva, Maria O.
Ortega-Carrion, Alvaro
Blanquez, Daniel
Arribas, Luis
Gomez, Carlos
Diez, Teresa
Pascual, Julio
Portero, Isabel
author_facet Portoles, Jose Maria
Jimenez, Carlos
Janeiro, Dario
Lopez-Oliva, Maria O.
Ortega-Carrion, Alvaro
Blanquez, Daniel
Arribas, Luis
Gomez, Carlos
Diez, Teresa
Pascual, Julio
Portero, Isabel
author_sort Portoles, Jose Maria
collection PubMed
description Immunosuppressive drugs are widely used to treat several autoimmune disorders and prevent rejection after organ transplantation. However, intra-individual variations in the pharmacological response to immunosuppressive therapy critically influence its efficacy, often resulting in poor treatment responses and serious side effects. Effective diagnostic tools that help clinicians to tailor immunosuppressive therapy to the needs and immunological profile of the individual patient thus constitute a major unmet clinical need. In vitro assays that measure immune cell responses to immunosuppressive drugs constitute a promising approach to individualized immunosuppressive therapy. Here, we present the Immunobiogram, a functional pharmacodynamic immune cell-based assay for simultaneous quantitative measurement of a patient’s immune response to a battery of immunosuppressive drugs. Peripheral blood mononuclear cells collected from patients are immunologically stimulated to induce activation and proliferation and embedded in a hydrogel mixture in which they are exposed to a concentration gradient of the immunosuppressants of interest. Analysis of samples from kidney transplant patients using this procedure revealed an association between the sensitivity of individual patients to the immunosuppressive regimen and their immunological risk of transplant rejection. Incorporation of the Immunobiogram assay into clinical settings could greatly facilitate personalized optimization and monitoring of immunosuppressive therapy, and study of the mechanisms underlying resistance to immunosuppressants.
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spelling pubmed-78685282021-02-09 The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy Portoles, Jose Maria Jimenez, Carlos Janeiro, Dario Lopez-Oliva, Maria O. Ortega-Carrion, Alvaro Blanquez, Daniel Arribas, Luis Gomez, Carlos Diez, Teresa Pascual, Julio Portero, Isabel Front Immunol Immunology Immunosuppressive drugs are widely used to treat several autoimmune disorders and prevent rejection after organ transplantation. However, intra-individual variations in the pharmacological response to immunosuppressive therapy critically influence its efficacy, often resulting in poor treatment responses and serious side effects. Effective diagnostic tools that help clinicians to tailor immunosuppressive therapy to the needs and immunological profile of the individual patient thus constitute a major unmet clinical need. In vitro assays that measure immune cell responses to immunosuppressive drugs constitute a promising approach to individualized immunosuppressive therapy. Here, we present the Immunobiogram, a functional pharmacodynamic immune cell-based assay for simultaneous quantitative measurement of a patient’s immune response to a battery of immunosuppressive drugs. Peripheral blood mononuclear cells collected from patients are immunologically stimulated to induce activation and proliferation and embedded in a hydrogel mixture in which they are exposed to a concentration gradient of the immunosuppressants of interest. Analysis of samples from kidney transplant patients using this procedure revealed an association between the sensitivity of individual patients to the immunosuppressive regimen and their immunological risk of transplant rejection. Incorporation of the Immunobiogram assay into clinical settings could greatly facilitate personalized optimization and monitoring of immunosuppressive therapy, and study of the mechanisms underlying resistance to immunosuppressants. Frontiers Media S.A. 2021-01-25 /pmc/articles/PMC7868528/ /pubmed/33569062 http://dx.doi.org/10.3389/fimmu.2020.618202 Text en Copyright © 2021 Portoles, Jimenez, Janeiro, Lopez-Oliva, Ortega-Carrion, Blanquez, Arribas, Gomez, Diez, Pascual and Portero http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Portoles, Jose Maria
Jimenez, Carlos
Janeiro, Dario
Lopez-Oliva, Maria O.
Ortega-Carrion, Alvaro
Blanquez, Daniel
Arribas, Luis
Gomez, Carlos
Diez, Teresa
Pascual, Julio
Portero, Isabel
The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title_full The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title_fullStr The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title_full_unstemmed The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title_short The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy
title_sort immunobiogram, a novel in vitro assay to evaluate treatment resistance in patients receiving immunosuppressive therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868528/
https://www.ncbi.nlm.nih.gov/pubmed/33569062
http://dx.doi.org/10.3389/fimmu.2020.618202
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