{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:14:19Z","timestamp":1791728059061,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022756","name":"Centre for Human Drug Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The recommended immunosuppressive treatment after kidney transplantation consists of tacrolimus, mycophenolate mofetil, and low\u2010dose corticosteroids. Drug concentrations are monitored using therapeutic drug monitoring (TDM), which does not necessarily correlate with pharmacodynamic activity. To find the balance between optimal efficacy and minimal toxicity, it might be more informative to monitor patients' immunological status rather than drug concentrations. We selected a panel of T\u2010cell\u2010based immune assays, which were used for immunomonitoring of 14 stable kidney transplantation patients. Whole blood was incubated with a T\u2010cell stimulus, after which T\u2010cell proliferation, T\u2010cell activation marker expression and cytokine production were measured to study residual immune activity in\u00a0vitro (before drug intake; drug added to the incubation) and ex\u00a0vivo (after drug intake). T\u2010cell proliferation was completely suppressed in all patients over the full day, while IL\u20102, IFN\u2010\u03b3, CD71, and CD154 showed fluctuations over the day with a strong inhibition (75%\u201325%) at 2\u2009h post\u2010dose. The level of inhibition was variable between patients and could not be related to pharmacokinetic parameters or the presence of regulatory or senescence immune cells. Moreover, the level of inhibition did not correlate with the in\u00a0vitro tacrolimus drug effect as studied by incubating pre\u2010dose blood samples with additional tacrolimus. Overall, IL\u20102, IFN\u2010\u03b3, CD71, and CD154 seem to be good markers to monitor residual immune activity of transplantation patients. To evaluate the correlation between these pharmacodynamic biomarkers and clinical outcome, prospective observational studies are needed.<\/jats:p>","DOI":"10.1111\/cts.13860","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T12:19:32Z","timestamp":1719317972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune responsiveness in stable kidney transplantation patients: Complete inhibition of T\u2010cell proliferation but residual T\u2010cell activity during maintenance immunosuppressive treatment"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6927-397X","authenticated-orcid":false,"given":"Aliede E.","family":"in\u00a0\u2019t\u00a0Veld","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-3122","authenticated-orcid":false,"given":"Boukje C.","family":"Eveleens\u00a0Maarse","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Juachon","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-8381","authenticated-orcid":false,"given":"Soufian","family":"Meziyerh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-3595","authenticated-orcid":false,"given":"Aiko P. 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