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

Jose Maria Portoles,Julio Pascual,Dario Janeiro,Isabel Portero,Maria O Lopez-Oliva,Luis Arribas,Alvaro Ortega-Carrion,Daniel Blanquez,Carlos Gomez,Carlos Jimenez,Teresa Diez

doi:10.3389/fimmu.2020.618202

Jose Maria Portoles, Julio Pascual + Show 9 more

Open Access

https://doi.org/10.3389/fimmu.2020.618202

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Abstract

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.

Highlights

Immunosuppressive (IS) medications that control and/or modulate the immune response are the treatment of choice for many inflammatory pathologies of autoimmune [1] and nonautoimmune origin, and are essential to prevent immunological graft rejection in transplant patients [2]
For the purpose of this analysis we focused on two parameters: Area Under the Curve (AUC) and IRMAX; a lower AUC value indicates reduced immune activity in the presence of the IMS, and a lower IRMAX indicates marked inhibition of cellular activation at maximal IMS concentration
Peripheral blood mononuclear cells (PBMCs) were obtained and assayed following the procedure described in the Materials and Methods (Figure 5)

Summary

Introduction

Immunosuppressive (IS) medications that control and/or modulate the immune response are the treatment of choice for many inflammatory pathologies of autoimmune [1] and nonautoimmune origin, and are essential to prevent immunological graft rejection in transplant patients [2] Their use in clinical practice has increased patient survival and quality of life and allowed for significant improvements in graft survival in transplant recipients [3]. The objective of immunosuppressive treatment is to restore the equilibrium of the immune system and/or the patient’s inflammatory state, thereby facilitating the development of physiological tissue repair mechanisms These beneficial effects are a consequence of partial silencing of the patient’s immune system, which is essential for life [4]. Adverse effects of immunosuppressive drugs and excess immunosuppression account for a large proportion of the mortality associated with immune-based inflammatory diseases [9, 10]

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