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

• Published in: Transplant immunology Vol. 75; p. 101711
• Main Authors: Pascual, Julio, Jiménez, Carlos, Krajewska, Magdalena, Seron, Daniel, Kotton, Camille N., Portolés, Jose, Witzke, Oliver, Sorensen, Soren S., Andrés, Amado, Crespo, Marta, Paz-Artal, Estela, Díez, Teresa, A., Ortega-Carrion, Portero, Isabel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-12-2022
• Subjects: Cellular pharmacodynamics immunosuppressive therapy monitoring; Immune cell assay; Transplant rejection; ESRD; STE; MTP; Transplant rejection; IMBG; AUC; CSA; ID50; RFUs; AOC; ABMR; ID75; OR; Immune cell assay; CI; GCC; ROC; AZA; KT; Cellular pharmacodynamics immunosuppressive therapy monitoring; PBMCs; PCC; GCP; TAC; dnDSA; ID25; SIR; EVER; MPA
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2022.101711

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.
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.
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).
Our results highlight the potential of Immunobiogram as a tool to test the pharmacodynamic response to individual immunosuppressive drugs.
•In-vitro measurement of patient's pharmacodynamic response to immunosuppressive drugs•A dose-response curve for patient and immunosuppressant tested•TRANSBIO: an observational, multicenter, international, exploratory study•Confirms association between drug-sensitivity and rejection after renal transplant