Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays
Mycophenolate mofetil (MMF) is part of the standard immunosuppressive treatment after transplantation and usually given as “one-dose-fits-all” together with a calcineurin inhibitor (CNI). Although drug concentrations are frequently monitored, there is still a group of patients who experience side ef...
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2023-05-01
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| author | Aliede E. in ’t Veld Manon A. A. Jansen Marieke L. de Kam Yalҫin Yavuz Dirk Jan A. R. Moes Kathalijne A. Oudhoff Mariette I. E. van Poelgeest Jacobus Burggraaf Matthijs Moerland |
| author_facet | Aliede E. in ’t Veld Manon A. A. Jansen Marieke L. de Kam Yalҫin Yavuz Dirk Jan A. R. Moes Kathalijne A. Oudhoff Mariette I. E. van Poelgeest Jacobus Burggraaf Matthijs Moerland |
| author_sort | Aliede E. in ’t Veld |
| collection | DOAJ |
| description | Mycophenolate mofetil (MMF) is part of the standard immunosuppressive treatment after transplantation and usually given as “one-dose-fits-all” together with a calcineurin inhibitor (CNI). Although drug concentrations are frequently monitored, there is still a group of patients who experience side effects related to excessive or insufficient immune suppression. We therefore aimed to identify biomarkers that reflect the overall immune status of the patient and might support individualized dosing. We previously studied immune biomarkers for CNIs and aimed to investigate whether these are also suitable to monitor MMF activity. Healthy volunteers received a single dose of MMF or placebo, after which IMPDH enzymatic activity, T cell proliferation, and cytokine production were measured and compared to MPA (MMF’s active metabolite) concentration in three different matrices (plasma, peripheral blood mononuclear cells, and T cells). MPA concentrations in T cells exceeded those in PBMCs, but all intracellular concentrations correlated strongly with plasma concentrations. At clinically relevant MPA concentrations, IL-2 and IFN-γ production was mildly suppressed, while MPA T cell proliferation was strongly inhibited. Based on these data, it is expected that monitoring of T cell proliferation in MMF-treated transplantation patients may be a valid strategy to avoid excessive immune suppression. |
| first_indexed | 2024-03-11T02:03:42Z |
| format | Article |
| id | doaj.art-e24bae55d78c4c8da0807e221b2ee5e1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T02:03:42Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e24bae55d78c4c8da0807e221b2ee5e12023-11-18T12:04:18ZengMDPI AGPharmaceutics1999-49232023-05-01156163510.3390/pharmaceutics15061635Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function AssaysAliede E. in ’t Veld0Manon A. A. Jansen1Marieke L. de Kam2Yalҫin Yavuz3Dirk Jan A. R. Moes4Kathalijne A. Oudhoff5Mariette I. E. van Poelgeest6Jacobus Burggraaf7Matthijs Moerland8Centre for Human Drug Research, 2233 CL Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsDepartment of Pharmacy and Clinical Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pharmacy and Clinical Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsCentre for Human Drug Research, 2233 CL Leiden, The NetherlandsMycophenolate mofetil (MMF) is part of the standard immunosuppressive treatment after transplantation and usually given as “one-dose-fits-all” together with a calcineurin inhibitor (CNI). Although drug concentrations are frequently monitored, there is still a group of patients who experience side effects related to excessive or insufficient immune suppression. We therefore aimed to identify biomarkers that reflect the overall immune status of the patient and might support individualized dosing. We previously studied immune biomarkers for CNIs and aimed to investigate whether these are also suitable to monitor MMF activity. Healthy volunteers received a single dose of MMF or placebo, after which IMPDH enzymatic activity, T cell proliferation, and cytokine production were measured and compared to MPA (MMF’s active metabolite) concentration in three different matrices (plasma, peripheral blood mononuclear cells, and T cells). MPA concentrations in T cells exceeded those in PBMCs, but all intracellular concentrations correlated strongly with plasma concentrations. At clinically relevant MPA concentrations, IL-2 and IFN-γ production was mildly suppressed, while MPA T cell proliferation was strongly inhibited. Based on these data, it is expected that monitoring of T cell proliferation in MMF-treated transplantation patients may be a valid strategy to avoid excessive immune suppression.https://www.mdpi.com/1999-4923/15/6/1635MMFmycophenolate mofetilMPAmycophenolic acidTDMtherapeutic drug monitoring |
| spellingShingle | Aliede E. in ’t Veld Manon A. A. Jansen Marieke L. de Kam Yalҫin Yavuz Dirk Jan A. R. Moes Kathalijne A. Oudhoff Mariette I. E. van Poelgeest Jacobus Burggraaf Matthijs Moerland Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays Pharmaceutics MMF mycophenolate mofetil MPA mycophenolic acid TDM therapeutic drug monitoring |
| title | Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays |
| title_full | Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays |
| title_fullStr | Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays |
| title_full_unstemmed | Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays |
| title_short | Immune Monitoring of Mycophenolate Mofetil Activity in Healthy Volunteers Using <i>Ex Vivo</i> T Cell Function Assays |
| title_sort | immune monitoring of mycophenolate mofetil activity in healthy volunteers using i ex vivo i t cell function assays |
| topic | MMF mycophenolate mofetil MPA mycophenolic acid TDM therapeutic drug monitoring |
| url | https://www.mdpi.com/1999-4923/15/6/1635 |
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