MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

Julian Stumpf; Torsten Siepmann; Jörg Schwöbel; Grit Glombig; Alexander Paliege; Anne Steglich; Florian Gembardt; Friederike Kessel; Hannah Kröger; Patrick Arndt; Jan Sradnick; Kerstin Frank; Anna Klimova; René Mauer; Torsten Tonn; Christian Hugo

doi:10.3389/fmed.2022.928542

MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

Julian Stumpf, Torsten Siepmann, Jörg Schwöbel, Grit Glombig, Alexander Paliege, Anne Steglich, Florian Gembardt, Friederike Kessel, Hannah Kröger, Patrick Arndt, Jan Sradnick, Kerstin Frank, Anna Klimova, René Mauer, Torsten Tonn, Christian Hugo

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7 Scopus citations

Abstract

Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

Original language	English (US)
Article number	928542
Journal	Frontiers in Medicine
Volume	9
DOIs	https://doi.org/10.3389/fmed.2022.928542
State	Published - Jul 7 2022
Externally published	Yes

Bibliographical note

Funding Information:
Members in alphabetical order within the corresponding centers: 1Medizinische Klinik und Poliklinik III, Universitätsklinikum, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Andrea Angermann, Nicole Bunk, Susanne Dollfus, Petya Drinova, Annegret Fleischer, Chris Gebauer, Susann Graichen, Kerstin Haaser, Sabrina Heide, Gabriele Hirt, Franziska Klemt, Markus Latk, Jens Passauer, Miriam Poser, Margrit Reinhardt, Ronny Rettig, Vladimir Todorov, Kerstin Zäumer 3KfH-Nierenzentrum am Klinikum Chemnitz, Krankenhaus Küchwald, Chemnitz, Germany Angela Grzegorek, Markus Hallmann, Saskia Härtwig, Christiane Hintzen-Kruse, Frauke Neidt und Söhne, Susann Reissland, Bianca Seidel, Anett Speer, Peggy Weiß, Christine Wiech 4Dialysezentrum Chemnitz, Chemnitz, Germany Markus Gläser, Ulrike Richardt, Anja Richter, Kathrin Scheibner, Andreas Sohn 5KfH-Nierenzentrum am Klinikum St. Georg, Leipzig, Germany Joachim Beige, Kathrin Heipmann, Claudia Karger, Christian Schauff, Peyo Kolev Sivenov 6PHV Dialysezentrum Dresden-Johannstadt, Dresden, Germany Steffen Bischoff, Petra Müller, Tatjana Seitz 8Institut für Transfusionsmedizin Plauen, DRK-Blutspendedienst Nord-Ost gemeinnützige GmbH, Plauen, Germany Nadine Hildebrandt, Andreas Karl. D. Michael Albrecht, Medizinischer Vorstand (Sprecher), Universitätsklinikum Carl Gustav Carus Dresden Thomas Grünewald, Chemnitz, Vorsitzender Sächsische Impfkommission Patricia Klein, Ärztliche Geschäftsführerin, Sächsische Landesärztekammer Körperschaft des öffentlichen Rechts Marcus Strotkötter, Senior Operations Officer for Vaccination Center and Mobile Vaccination Teams at DRK Landesverband Sachsen e.V. EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany provided antibody ELISAs and interferon-gamma release assays for this study.

Funding Information:
This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27 and the “Sächsisches Staatsministerium für Wissenschaft, Kultur und Tourismus” via Sächsische AufbauBank, grant number (SAB-Antragsnr). (100592538).

Publisher Copyright:
Copyright © 2022 Stumpf, Siepmann, Schwöbel, Glombig, Paliege, Steglich, Gembardt, Kessel, Kröger, Arndt, Sradnick, Frank, Klimova, Mauer, Tonn and Hugo.

Keywords

SARS-CoV-2
clinical decision making
guidelines
humoral response
kidney transplant recipients
mycophenolic acid
vaccination

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fmed.2022.928542

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Cite this

Stumpf, J., Siepmann, T., Schwöbel, J., Glombig, G., Paliege, A., Steglich, A., Gembardt, F., Kessel, F., Kröger, H., Arndt, P., Sradnick, J., Frank, K., Klimova, A., Mauer, R., Tonn, T., & Hugo, C. (2022). MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination. Frontiers in Medicine, 9, Article 928542. https://doi.org/10.3389/fmed.2022.928542

Stumpf, J, Siepmann, T, Schwöbel, J, Glombig, G, Paliege, A, Steglich, A, Gembardt, F, Kessel, F, Kröger, H, Arndt, P, Sradnick, J, Frank, K, Klimova, A, Mauer, R, Tonn, T & Hugo, C 2022, 'MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination', Frontiers in Medicine, vol. 9, 928542. https://doi.org/10.3389/fmed.2022.928542

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title = "MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination",

abstract = "Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.",

keywords = "SARS-CoV-2, clinical decision making, guidelines, humoral response, kidney transplant recipients, mycophenolic acid, vaccination",

author = "Julian Stumpf and Torsten Siepmann and J{\"o}rg Schw{\"o}bel and Grit Glombig and Alexander Paliege and Anne Steglich and Florian Gembardt and Friederike Kessel and Hannah Kr{\"o}ger and Patrick Arndt and Jan Sradnick and Kerstin Frank and Anna Klimova and Ren{\'e} Mauer and Torsten Tonn and Christian Hugo",

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doi = "10.3389/fmed.2022.928542",

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T1 - MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

AU - Stumpf, Julian

AU - Siepmann, Torsten

AU - Schwöbel, Jörg

AU - Glombig, Grit

AU - Paliege, Alexander

AU - Steglich, Anne

AU - Gembardt, Florian

AU - Kessel, Friederike

AU - Kröger, Hannah

AU - Arndt, Patrick

AU - Sradnick, Jan

AU - Frank, Kerstin

AU - Klimova, Anna

AU - Mauer, René

AU - Tonn, Torsten

AU - Hugo, Christian

N1 - Funding Information: Members in alphabetical order within the corresponding centers: 1Medizinische Klinik und Poliklinik III, Universitätsklinikum, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Andrea Angermann, Nicole Bunk, Susanne Dollfus, Petya Drinova, Annegret Fleischer, Chris Gebauer, Susann Graichen, Kerstin Haaser, Sabrina Heide, Gabriele Hirt, Franziska Klemt, Markus Latk, Jens Passauer, Miriam Poser, Margrit Reinhardt, Ronny Rettig, Vladimir Todorov, Kerstin Zäumer 3KfH-Nierenzentrum am Klinikum Chemnitz, Krankenhaus Küchwald, Chemnitz, Germany Angela Grzegorek, Markus Hallmann, Saskia Härtwig, Christiane Hintzen-Kruse, Frauke Neidt und Söhne, Susann Reissland, Bianca Seidel, Anett Speer, Peggy Weiß, Christine Wiech 4Dialysezentrum Chemnitz, Chemnitz, Germany Markus Gläser, Ulrike Richardt, Anja Richter, Kathrin Scheibner, Andreas Sohn 5KfH-Nierenzentrum am Klinikum St. Georg, Leipzig, Germany Joachim Beige, Kathrin Heipmann, Claudia Karger, Christian Schauff, Peyo Kolev Sivenov 6PHV Dialysezentrum Dresden-Johannstadt, Dresden, Germany Steffen Bischoff, Petra Müller, Tatjana Seitz 8Institut für Transfusionsmedizin Plauen, DRK-Blutspendedienst Nord-Ost gemeinnützige GmbH, Plauen, Germany Nadine Hildebrandt, Andreas Karl. D. Michael Albrecht, Medizinischer Vorstand (Sprecher), Universitätsklinikum Carl Gustav Carus Dresden Thomas Grünewald, Chemnitz, Vorsitzender Sächsische Impfkommission Patricia Klein, Ärztliche Geschäftsführerin, Sächsische Landesärztekammer Körperschaft des öffentlichen Rechts Marcus Strotkötter, Senior Operations Officer for Vaccination Center and Mobile Vaccination Teams at DRK Landesverband Sachsen e.V. EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany provided antibody ELISAs and interferon-gamma release assays for this study. Funding Information: This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27 and the “Sächsisches Staatsministerium für Wissenschaft, Kultur und Tourismus” via Sächsische AufbauBank, grant number (SAB-Antragsnr). (100592538). Publisher Copyright: Copyright © 2022 Stumpf, Siepmann, Schwöbel, Glombig, Paliege, Steglich, Gembardt, Kessel, Kröger, Arndt, Sradnick, Frank, Klimova, Mauer, Tonn and Hugo.

PY - 2022/7/7

Y1 - 2022/7/7

N2 - Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

AB - Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.

KW - SARS-CoV-2

KW - clinical decision making

KW - guidelines

KW - humoral response

KW - kidney transplant recipients

KW - mycophenolic acid

KW - vaccination

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MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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