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

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  • Julio Pascual
  • Carlos Jiménez
  • Magdalena Krajewska
  • Daniel Seron
  • Camille N. Kotton
  • Jose Portolés
  • Oliver Witzke
  • Sørensen, Søren Schwartz
  • Amado Andrés
  • Marta Crespo
  • Estela Paz-Artal
  • Teresa Díez
  • Alvaro Ortega
  • Isabel Portero

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
ISSN0966-3274
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
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 ).

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