The Immunobiogram,a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients |
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| Affiliation: | 1. Nephrology Department, Hospital del Mar, Institute Mar for Medical Research, Barcelona, Spain;2. Nephrology Department, Hospital 12 de Octubre, Madrid, Spain;3. Nephrology Department, Hospital La Paz, Madrid, Spain;4. Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland;5. Nephrology Department, Hospital Vall d''Hebron, Barcelona, Spain;6. Transplant Infectious Diseases Division, Massachusetts General Hospital, Boston, MA, United States of America;7. Nephrology Department, Hospital Puerta de Hierro, Madrid, Spain;8. Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany;9. Department of Nephrology, Rigshospitalet University Hospital Copenhagen, Denmark;10. Immunology Department, Hospital 12 de Octubre, Madrid, Spain;11. Biohope Scientific Solutions for Human Health, Madrid, Spain |
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| Abstract: | BackgroundDiagnostic 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.MethodsWe 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.ResultsClinical 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).ConclusionsOur results highlight the potential of Immunobiogram as a tool to test the pharmacodynamic response to individual immunosuppressive drugs. |
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