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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doaj-3bc5736d6a1b484ca6c8e5e858a3be3a2021-01-25T12:42:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.618202618202The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive TherapyJose Maria Portoles0Jose Maria Portoles1Carlos Jimenez2Carlos Jimenez3Dario Janeiro4Dario Janeiro5Maria O. Lopez-Oliva6Maria O. Lopez-Oliva7Alvaro Ortega-Carrion8Daniel Blanquez9Luis Arribas10Carlos Gomez11Teresa Diez12Julio Pascual13Julio Pascual14Isabel Portero15Department of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, SpainResearch net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, SpainResearch net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, SpainDepartment of Nephrology, Hospital La Paz, Madrid, SpainDepartment of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, SpainResearch net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, SpainResearch net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, SpainDepartment of Nephrology, Hospital La Paz, Madrid, SpainR+D Department, BIOHOPE Scientific SL, Madrid, SpainAdamas Engineering Consulting, Madrid, SpainAdamas Engineering Consulting, Madrid, SpainR+D Department, BIOHOPE Scientific SL, Madrid, SpainR+D Department, BIOHOPE Scientific SL, Madrid, SpainResearch net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, SpainDepartment of Nephrology, Hospital del Mar, Institut Mar for Medical Research, Barcelona, SpainR+D Department, BIOHOPE Scientific SL, Madrid, SpainImmunosuppressive 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.618202/fullcellular pharmacodynamicsimmune cell assayimmunosuppressive therapy monitoringtransplant rejectionpersonalized medicine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jose Maria Portoles Jose Maria Portoles Carlos Jimenez Carlos Jimenez Dario Janeiro Dario Janeiro Maria O. Lopez-Oliva Maria O. Lopez-Oliva Alvaro Ortega-Carrion Daniel Blanquez Luis Arribas Carlos Gomez Teresa Diez Julio Pascual Julio Pascual Isabel Portero |
spellingShingle |
Jose Maria Portoles Jose Maria Portoles Carlos Jimenez Carlos Jimenez Dario Janeiro Dario Janeiro Maria O. Lopez-Oliva Maria O. Lopez-Oliva Alvaro Ortega-Carrion Daniel Blanquez Luis Arribas Carlos Gomez Teresa Diez Julio Pascual Julio Pascual Isabel Portero The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy Frontiers in Immunology cellular pharmacodynamics immune cell assay immunosuppressive therapy monitoring transplant rejection personalized medicine |
author_facet |
Jose Maria Portoles Jose Maria Portoles Carlos Jimenez Carlos Jimenez Dario Janeiro Dario Janeiro Maria O. Lopez-Oliva Maria O. Lopez-Oliva Alvaro Ortega-Carrion Daniel Blanquez Luis Arribas Carlos Gomez Teresa Diez Julio Pascual Julio Pascual Isabel Portero |
author_sort |
Jose Maria Portoles |
title |
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_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_sort |
immunobiogram, a novel in vitro assay to evaluate treatment resistance in patients receiving immunosuppressive therapy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-01-01 |
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. |
topic |
cellular pharmacodynamics immune cell assay immunosuppressive therapy monitoring transplant rejection personalized medicine |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.618202/full |
work_keys_str_mv |
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