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, 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
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.
Keywords: Cellular pharmacodynamics immunosuppressive therapy monitoring; Immune cell assay; Transplant rejection.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Source: PubMed