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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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Article

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

Publicated to:TRANSPLANT IMMUNOLOGY. 75 101711- - 2022-12-01 75(), DOI: 10.1016/j.trim.2022.101711

Authors: Pascual, Julio; Jimenez, Carlos; Krajewska, Magdalena; Seron, Daniel; Kotton, Camille N.; Portoles, Jose; Witzke, Oliver; Sorensen, Soren S.; Andres, Amado; Crespo, Marta; Paz-Artal, Estela; Diez, Teresa; Ortega, Alvaro; Portero, Isabel;

Affiliations

Biohope Sci Solut Human Hlth, Madrid, Spain - Author
Hosp 12 Octubre, Immunol Dept, Madrid, Spain - Author
Hosp 12 Octubre, Nephrol Dept, Madrid, Spain - Author
Hosp La Paz, Nephrol Dept, Madrid, Spain - Author
Hosp Mar, Inst Mar Med Res, Nephrol Dept, Barcelona, Spain - Author
Hosp Puerta Hierro, Nephrol Dept, Madrid, Spain - Author
Hosp Valle De Hebron, Nephrol Dept, Barcelona, Spain - Author
Massachusetts Gen Hosp, Transplant Infect Dis Div, Boston, MA 02114 USA - Author
Univ Duisburg Essen, Univ Hosp Essen, Dept Infect Dis, Essen, Germany - Author
Univ Hosp Copenhagen, Dept Nephrol, Rigshosp, Copenhagen, Denmark - Author
Wroclaw Med Univ, Dept Nephrol & Transplantat Med, Wroclaw, Poland - Author
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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 monitoringimmune cell assayCellular pharmacodynamicsConsensusCyclosporineDnaDrugsFailureImmune cell assayImmunosuppressive therapy monitoringManagementRecipientsRejectionTransplant rejection

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal TRANSPLANT IMMUNOLOGY, and although the journal is classified in the quartile Q4 (Agencia WoS (JCR)), its regional focus and specialization in Immunology, give it significant recognition in a specific niche of scientific knowledge at an international level.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.62, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-16, the following number of citations:

  • WoS: 2
  • Scopus: 3
  • OpenCitations: 6

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 7.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 7 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.5.
  • The number of mentions on the social network X (formerly Twitter): 13 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Denmark; Germany; Poland; United States of America.