The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients

Julio Pascual*, Carlos Jiménez, Magdalena Krajewska, Daniel Seron, Camille N Kotton, Jose Portolés, Oliver Witzke, Soren S Sorensen, Amado Andrés, Marta Crespo, Estela Paz-Artal, Teresa Díez, Alvaro Ortega, Isabel Portero

*Corresponding author af dette arbejde
    2 Citationer (Scopus)

    Abstract

    BACKGROUND: Diagnostic tools to measure the response to individual immunosuppressive drugs for transplant patients are currently lacking. We previously developed the blood-based Immunobiogram bioassay for in-vitro characterization of the pharmacodynamic response of patients' own immune cells to a range of immunosuppressants. We used Immunobiogram to examine the association between patients' sensitivity to their prescribed immunosuppressants and clinical outcome.

    METHODS: We conducted an international, multicenter, observational study in a kidney transplant population undergoing maintenance immunosuppressive therapy. Patients were selected by clinical course (poor [PCC] N = 53 (with renal dysfunction, and rejection signs in biopsy or/and an increase in DSA strength in last 12 months) versus good [GCC] N = 50 (with stable renal function and treatment, no rejection and no DSA titers). Immunobiogram dose-response curve parameters were compared between both subgroups in patients treated with mycophenolate, tacrolimus, corticosteroids, cyclosporine A or everolimus. Parameters for which significant inter-group differences were observed were further analyzed by univariate and subsequent multivariate logistic regression.

    RESULTS: Clinical outcome was associated with following parameters: area over the curve (AOC) and 25% (ID25) and 50% (ID50) inhibitory response in mycophenolate, tacrolimus, and corticosteroid-treated subgroups, respectively. These statistically significant associations persisted in mycophenolate (OR 0.003, CI95% <0.001-0.258; p = 0.01) and tacrolimus (OR < 0.0001, CI95% <0.00001-0.202; p = 0.016) subgroups after adjusting for concomitant corticosteroid treatment, and in corticosteroid subgroup after adjusting for concomitant mycophenolate or tacrolimus treatment (OR 0.003; CI95% <0.0001-0.499; p = 0.026).

    CONCLUSIONS: Our results highlight the potential of Immunobiogram as a tool to test the pharmacodynamic response to individual immunosuppressive drugs.

    OriginalsprogEngelsk
    Artikelnummer101711
    TidsskriftTransplant Immunology
    Vol/bind75
    Antal sider9
    ISSN0966-3274
    DOI
    StatusUdgivet - 2022

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