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

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  • dc.contributor.author Pascual Santos, Julio
  • dc.contributor.author Jiménez, Carlos
  • dc.contributor.author Krajewska, Magdalena
  • dc.contributor.author Seron, Daniel
  • dc.contributor.author Kotton, Camille N.
  • dc.contributor.author Portolés, José
  • dc.contributor.author Witzke, Oliver
  • dc.contributor.author Sorensen, Soren S.
  • dc.contributor.author Andrés, Amado
  • dc.contributor.author Crespo Barrio, Marta
  • dc.contributor.author Paz-Artal, Estela
  • dc.contributor.author Díez, Teresa
  • dc.contributor.author Ortega, Álvaro
  • dc.contributor.author Portero, Isabel
  • dc.date.accessioned 2023-02-16T07:10:50Z
  • dc.date.available 2023-02-16T07:10:50Z
  • dc.date.issued 2022
  • dc.description.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.
  • dc.description.sponsorship Research was funded by a competitive grant from the European Commission (SME Instrument – Phase II), Project: TRANSBIO (Id 733248) “Cellular BIOtechnology for prognosis and monitoring in renal TRANSplantation” (https://cordis.europa.eu/project/id/733248).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pascual J, Jiménez C, Krajewska M, Seron D, Kotton CN, Portolés J, Witzke O, Sorensen SS, Andrés A, Crespo M, Paz-Artal E, Díez T, Ortega A, Portero I. The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients. Transpl Immunol. 2022 Dec;75:101711. DOI: 10.1016/j.trim.2022.101711
  • dc.identifier.doi http://dx.doi.org/10.1016/j.trim.2022.101711
  • dc.identifier.issn 0966-3274
  • dc.identifier.uri http://hdl.handle.net/10230/55802
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Transpl Immunol. 2022 Dec;75:101711
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733248
  • dc.rights © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Cellular pharmacodynamics immunosuppressive therapy monitoring
  • dc.subject.keyword Immune cell assay
  • dc.subject.keyword Transplant rejection
  • dc.title The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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