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2. Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

Author

Stich, Maximilian, Di Cristanziano, Veronica, Tönshoff, Burkhard, Weber, Lutz Thorsten, Dötsch, Jörg, Rammer, Marian Theodor, Rieger, Susanne, Heger, Eva, Garbade, Sven F., Burgmaier, Kathrin, Benning, Louise, Speer, Claudius, Habbig, Sandra, and Haumann, Sophie

Published
2023
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3. Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients

Author

Benning, Louise, Morath, Christian, Bartenschlager, Marie, Kim, Heeyoung, Reineke, Marvin, Beimler, Jörg, Buylaert, Mirabel, Nusshag, Christian, Kälble, Florian, Reichel, Paula, Töllner, Maximilian, Schaier, Matthias, Klein, Katrin, Benes, Vladimir, Rausch, Tobias, Rieger, Susanne, Stich, Maximilian, Tönshoff, Burkhard, Weidner, Niklas, Schnitzler, Paul, Zeier, Martin, Süsal, Caner, Hien Tran, Thuong, Bartenschlager, Ralf, and Speer, Claudius

Published
2022
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4. Impact of deceased-donor characteristics on early graft function: outcome of kidney donor pairs accepted for transplantation.

Author

Mahler, Christoph F., Friedl, Felix, Nusshag, Christian, Speer, Claudius, Benning, Louise, Göth, Daniel, Schaier, Matthias, Sommerer, Claudia, Mieth, Markus, Mehrabi, Arianeb, Renders, Lutz, Heemann, Uwe, Krautter, Markus, Schwenger, Vedat, Echterdiek, Fabian, Zeier, Martin, Morath, Christian, and Kälble, Florian

Subjects
GENERALIZED estimating equations, GRAFT survival, GLOMERULAR filtration rate, BODY mass index, KIDNEY transplantation
Abstract

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals. Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure. Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors. Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics. [ABSTRACT FROM AUTHOR]

Published
2024
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6. #569 Proenkephalin A 119-159 (penKid) for the early identification and risk stratification of delayed graft function following kidney transplantation

Author

Benning, Louise, primary, Reineke, Marvin, additional, Kälble, Florian, additional, Speer, Claudius, additional, Göth, Daniel, additional, Hartmann, Oliver, additional, Mieth, Markus, additional, Zeier, Martin, additional, Mehrabi, Arianeb, additional, Weigand, Markus A, additional, Morath, Christian, additional, and Nusshag, Christian, additional

Published
2024
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7. The balance between memory and regulatory cell populations in kidney transplant recipients with operational tolerance

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Alvarez, Cristiam M.; Benning, Louise; Daniel, Volker; Zeier, Martin; Schaier, Matthias; Morath, Christian; Speer, Claudius, Koç University Transplant Immunology Research Centre of Excellence (TIREX), Koç University Hospital, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Alvarez, Cristiam M.; Benning, Louise; Daniel, Volker; Zeier, Martin; Schaier, Matthias; Morath, Christian; Speer, Claudius, Koç University Transplant Immunology Research Centre of Excellence (TIREX), Koç University Hospital, and School of Medicine

Abstract

Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N=8), chronic rejection (N=8), and different immunosuppressive treatment regimens (N=81). Patients on hemodialysis and healthy individuals served as controls (N=50). In addition, the expression of Treg- and Breg-associated molecule genes was analyzed. Patients with chronic rejection showed a disrupted memory T cell composition with a significantly higher frequency of circulating CD8(+) terminally differentiated effector memory (TEMRA) T cells than patients with operational tolerance, patients on hemodialysis, or healthy controls (P<0.001). Low frequency of CD8(+) TEMRA and high frequency of Tregs and transitional Bregs were found in operationally tolerant patients. Consequently, operationally tolerant patients showed, as compared to all other transplant recipients with different immunosuppressive regiments, the lowest ratios between CD8(+) TEMRA T cells and Tregs or Bregs (for both P<0.001). Moreover, a specific peripheral blood transcription pattern was found in operationally tolerant patients with an increased expression of Breg- and Treg-associated genes CD22 and FoxP3 and a decreased Fc gamma RIIA/Fc gamma RIIB transcript ratio (for all P<0.001). In conclusion, monitoring the balance between circulating CD8(+) TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with operational tolerance from recipients at risk of graft loss., European Union (EU); Horizon 2020; Research and Innovation Programme; Physician Scientist Program of the Heidelberg Faculty of Medicine; Olympia-Morata Program of the Heidelberg Faculty of Medicine

Published
2024

8. Durability of Humoral Responses after an Adapted SARS-CoV-2 mRNA Vaccine Dose in Hemodialysis Patients.

Author

Benning, Louise, Bartenschlager, Marie, Kim, Heeyoung, Morath, Christian, Zeier, Martin, Schnitzler, Paul, Bartenschlager, Ralf, and Speer, Claudius

Subjects
BOOSTER vaccines, COVID-19 vaccines, HUMORAL immunity, BREAKTHROUGH infections, HEMODIALYSIS patients
Abstract

We recently showed that an adapted SARS-CoV-2 vaccine with wildtype and BA.4/BA.5 Omicron subtype epitopes induced a broad short-term immune response in hemodialysis patients. Antibodies with protective capacity were boosted significantly after a follow-up period of 3 weeks following a fifth vaccine dose. However, data on the longevity of the humoral response after bivalent vaccination are lacking but urgently needed to make recommendations for further booster vaccinations in this patient group. This study is an extension of our previously published data including 40 patients on hemodialysis with a follow-up period of 12 months after an adapted booster vaccine dose. We performed a detailed characterization of humoral immune responses and assessed breakthrough infections. In addition, the severity of breakthrough infections was assessed using an established grading system. Anti-S1 IgG and surrogate neutralizing antibodies significantly decreased during the period of 12 months (p < 0.01 and p < 0.001, respectively). Live-virus neutralizing antibodies against the wildtype and the BA.5 subtype also significantly decreased over time (p < 0.01 and p < 0.01, respectively). However, even 12 months after administration of the adapted vaccine dose, all 40/40 (100%) of hemodialysis patients showed detectable SARS-CoV-2 wildtype neutralization activity, with 35/40 (88%) also exhibiting detectable BA.5 subtype neutralization activity. During follow-up, 13/40 (33%) patients contracted a SARS-CoV-2 breakthrough infection, among which 12 cases were categorized as asymptomatic or mild, while only 1 case was classified as moderate disease activity. Thus, bivalent booster vaccination seems to induce a sustained immune response in hemodialysis patients over a period of 12 months with breakthrough infections occurring frequently but predominantly manifesting as asymptomatic or mild. [ABSTRACT FROM AUTHOR]

Published
2024
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9. The balance between memory and regulatory cell populations in kidney transplant recipients with operational tolerance.

Author

Süsal, Caner, Alvarez, Cristiam M, Benning, Louise, Daniel, Volker, Zeier, Martin, Schaier, Matthias, Morath, Christian, and Speer, Claudius

Subjects
CELL populations, REGULATORY T cells, REGULATORY B cells, IMMUNOLOGIC memory, KIDNEY transplantation, PROSPECTIVE memory, PAIN tolerance
Abstract

Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T-cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N = 8), chronic rejection (N = 8), and different immunosuppressive treatment regimens (N = 81). Patients on hemodialysis and healthy individuals served as controls (N = 50). In addition, the expression of Treg- and Breg-associated molecule genes was analyzed. Patients with chronic rejection showed a disrupted memory T-cell composition with a significantly higher frequency of circulating CD8+ terminally differentiated effector memory (TEMRA) T cells than patients with operational tolerance, patients on hemodialysis, or healthy controls (P < 0.001). Low frequency of CD8+ TEMRA and high frequency of Tregs and transitional Bregs were found in operationally tolerant patients. Consequently, operationally tolerant patients showed, as compared to all other transplant recipients with different immunosuppressive regiments, the lowest ratios between CD8+ TEMRA T cells and Tregs or Bregs (for both P < 0.001). Moreover, a specific peripheral blood transcription pattern was found in operationally tolerant patients with an increased expression of Breg- and Treg-associated genes CD22 and FoxP3 and a decreased FcγRIIA/FcγRIIB transcript ratio (for all P < 0.001). In conclusion, monitoring the balance between circulating CD8+ TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with operational tolerance from recipients at risk of graft loss. We show that a balance between effector mechanisms mediated by CD8 + TEMRA T cells and regulatory cell populations such as Bregs, Tregs, or naive T cells determines long-term kidney graft survival. Monitoring the balance between circulating CD8 + TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with OT from recipients at risk of graft loss. Our study provides evidence in favor of regulatory mechanisms that counterbalance alloreactive memory immune responses and may encourage further investigations whether the ratio between CD8 + TEMRA T cells and Tregs or Bregs can help to safely guide minimization of immunosuppression in selected patients. Graphical Abstract [ABSTRACT FROM AUTHOR]

Published
2024
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10. Dynamics of torque teno virus load in kidney transplant recipients with indication biopsy and therapeutic modifications of immunosuppression

Author

Reineke, Marvin, primary, Morath, Christian, additional, Speer, Claudius, additional, Rudek, Markus, additional, Bundschuh, Christian, additional, Klein, Julian A.F., additional, Mahler, Christoph F., additional, Kälble, Florian, additional, Nusshag, Christian, additional, Beimler, Jörg, additional, Zeier, Martin, additional, Bartenschlager, Ralf, additional, Schnitzler, Paul, additional, and Benning, Louise, additional

Published
2024
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11. Live‐virus serum neutralization after bivalent SARS‐CoV‐2 mRNA vaccination in hemodialysis patients

Author

Benning, Louise, primary, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Kälble, Florian, additional, Nusshag, Christian, additional, Buylaert, Mirabel, additional, Reichel, Paula, additional, Schaier, Matthias, additional, Morath, Christian, additional, Zeier, Martin, additional, Schnitzler, Paul, additional, Bartenschlager, Ralf, additional, and Speer, Claudius, additional

Published
2023
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12. Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy—Results of a Prospective Single-Center Trial

Author

Benning, Louise, primary, Morath, Christian, additional, Fink, Annette, additional, Rudek, Markus, additional, Speer, Claudius, additional, Kälble, Florian, additional, Nusshag, Christian, additional, Beimler, Jörg, additional, Schwab, Constantin, additional, Waldherr, Rüdiger, additional, Zeier, Martin, additional, Süsal, Caner, additional, and Tran, Thuong Hien, additional

Published
2023
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14. BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study

Author

Speer, Claudius, primary, Töllner, Maximilian, additional, Benning, Louise, additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reineke, Marvin, additional, Reichel, Paula, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Morath, Christian, additional, Schmitt, Wilhelm, additional, Bergner, Raoul, additional, Bartenschlager, Ralf, additional, Lorenz, Hanns-Martin, additional, and Schaier, Matthias, additional

Published
2023
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15. Liver-Support Therapies in Critical Illness—A Comparative Analysis of Procedural Characteristics and Safety

Author

Göth, Daniel, primary, Mahler, Christoph F., additional, Kälble, Florian, additional, Speer, Claudius, additional, Benning, Louise, additional, Schmitt, Felix C. F., additional, Dietrich, Maximilian, additional, Krautkrämer, Ellen, additional, Zeier, Martin, additional, Merle, Uta, additional, Morath, Christian, additional, Fiedler, Mascha O., additional, Weigand, Markus A., additional, and Nusshag, Christian, additional

Published
2023
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16. Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation

Author

Schaier, Matthias, primary, Morath, Christian, additional, Wang, Lei, additional, Kleist, Christian, additional, Opelz, Gerhard, additional, Tran, Thuong Hien, additional, Scherer, Sabine, additional, Pham, Lien, additional, Ekpoom, Naruemol, additional, Süsal, Caner, additional, Ponath, Gerald, additional, Kälble, Florian, additional, Speer, Claudius, additional, Benning, Louise, additional, Nusshag, Christian, additional, Mahler, Christoph F., additional, Pego da Silva, Luiza, additional, Sommerer, Claudia, additional, Hückelhoven-Krauss, Angela, additional, Czock, David, additional, Mehrabi, Arianeb, additional, Schwab, Constantin, additional, Waldherr, Rüdiger, additional, Schnitzler, Paul, additional, Merle, Uta, additional, Schwenger, Vedat, additional, Krautter, Markus, additional, Kemmner, Stephan, additional, Fischereder, Michael, additional, Stangl, Manfred, additional, Hauser, Ingeborg A., additional, Kälsch, Anna-Isabelle, additional, Krämer, Bernhard K., additional, Böhmig, Georg A., additional, Müller-Tidow, Carsten, additional, Reiser, Jochen, additional, Zeier, Martin, additional, Schmitt, Michael, additional, Terness, Peter, additional, Schmitt, Anita, additional, and Daniel, Volker, additional

Published
2023
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17. Donor-derived cell-free DNA (dd-cfDNA) in kidney transplant recipients with indication biopsy-results of a prospective single-center trial

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Fink, Annette; Rudek, Markus; Speer, Claudius; Kaelble, Florian; Nusshag, Christian; Beimler, Joerg; Schwab, Constantin; Waldherr, Ruediger; Zeier, Martin; Tran, Thuong Hien, Koç University Transplant Immunology Research Centre of Excellence (TIREX), Koç University Hospital, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Fink, Annette; Rudek, Markus; Speer, Claudius; Kaelble, Florian; Nusshag, Christian; Beimler, Joerg; Schwab, Constantin; Waldherr, Ruediger; Zeier, Martin; Tran, Thuong Hien, Koç University Transplant Immunology Research Centre of Excellence (TIREX), Koç University Hospital, and School of Medicine

Abstract

Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology. Additionally, dd-cfDNA was determined on days 7, 30, and 90 post-biopsy and analyzed for potential use to monitor response to anti-rejection treatment. dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48-3.20) highest in patients with ABMR, followed by 0.92 (0.19-11.25) in patients with TCMR, 0.44 (0.20-1.10) in patients with borderline changes and 0.20 (0.11-0.53) in patients with no signs of rejection. The AUC for dd-cfDNA to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62-0.83). In patients receiving anti-rejection treatment, dd-cfDNA levels significantly decreased during the 7, 30, and 90 days follow-up compared to levels at the time of biopsy (p = 0.006, p = 0.002, and p < 0.001, respectively). In conclusion, dd-cfDNA significantly discriminates active rejection from no rejection. Decreasing dd-cfDNA following anti-rejection treatment may indicate response to therapy., European Union (EU); Horizon 2020; Research and Innovation Programme; LB is funded by the Olympia Morata Program of Heidelberg University. CSp is funded by the Physician Scientist Program of the Heidelberg Faculty of Medicine. For the publication fee we acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding program “Open Access Publikationskosten” as well as by Heidelberg University.

Published
2023

19. Live‐virus neutralization of the omicron variant in children and adults 14 months after SARS‐CoV‐2 wild‐type infection

Author

Stich, Maximilian, primary, Benning, Louise, additional, Speer, Claudius, additional, Garbade, Sven F., additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Jeltsch, Kathrin, additional, Tabatabai, Julia, additional, Niesert, Moritz, additional, Janda, Aleš, additional, Renk, Hanna, additional, Elling, Roland, additional, Hoffmann, Georg Friedrich, additional, Kräusslich, Hans‐Georg, additional, Müller, Barbara, additional, Bartenschlager, Ralf, additional, and Tönshoff, Burkhard, additional

Published
2023
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20. Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose

Author

Kühn, Tessa, primary, Speer, Claudius, additional, Morath, Christian, additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Beimler, Jörg, additional, Buylaert, Mirabel, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reineke, Marvin, additional, Töllner, Maximilian, additional, Klein, Katrin, additional, Blank, Antje, additional, Parthé, Sylvia, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Bartenschlager, Ralf, additional, Tran, Thuong Hien, additional, Schaier, Matthias, additional, and Benning, Louise, additional

Published
2023
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21. Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

Author

Stich, Maximilian, primary, Di Cristanziano, Veronica, additional, Tönshoff, Burkhard, additional, Weber, Lutz Thorsten, additional, Dötsch, Jörg, additional, Rammer, Marian Theodor, additional, Rieger, Susanne, additional, Heger, Eva, additional, Garbade, Sven F., additional, Burgmaier, Kathrin, additional, Benning, Louise, additional, Speer, Claudius, additional, Habbig, Sandra, additional, and Haumann, Sophie, additional

Published
2022
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22. Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): protocol for a multicentre, open-label, phase II, randomised controlled trial

Author

Morath, Christian, primary, Schmitt, Anita, additional, Schmitt, Michael, additional, Wang, Lei, additional, Kleist, Christian, additional, Opelz, Gerhard, additional, Süsal, Caner, additional, Tran, T. Hien, additional, Scherer, Sabine, additional, Schwenger, Vedat, additional, Kemmner, Stephan, additional, Fischereder, Michael, additional, Stangl, Manfred, additional, Hauser, Ingeborg A., additional, Sommerer, Claudia, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Speer, Claudius, additional, Benning, Louise, additional, Bischofs, Christian, additional, Sauer, Sandra, additional, Schubert, Maria-Luisa, additional, Kunz, Alexander, additional, Hückelhoven-Krauss, Angela, additional, Neuber, Brigitte, additional, Mehrabi, Arianeb, additional, Schwab, Constantin, additional, Waldherr, Rüdiger, additional, Sander, Anja, additional, Büsch, Christopher, additional, Czock, David, additional, Böhmig, Georg A, additional, Reiser, Jochen, additional, Roers, Axel, additional, Müller-Tidow, Carsten, additional, Terness, Peter, additional, Zeier, Martin, additional, Daniel, Volker, additional, and Schaier, Matthias, additional

Published
2022
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23. Waning Immunity 14 Months After SARS-CoV-2 Infection

Author

Stich, Maximilian, primary, Benning, Louise, additional, Speer, Claudius, additional, Garbade, Sven F., additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Gleich, Florian, additional, Jeltsch, Kathrin, additional, Haase, Bettina, additional, Janda, Aleš, additional, Renk, Hanna, additional, Elling, Roland, additional, Schnitzler, Paul, additional, Waterboer, Tim, additional, Hoffmann, Georg Friedrich, additional, Kräusslich, Hans-Georg, additional, Müller, Barbara, additional, Bartenschlager, Ralf, additional, and Tönshoff, Burkhard, additional

Published
2022
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24. Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients

Author

Morath, Christian, primary, Schaier, Matthias, additional, Ibrahim, Eman, additional, Wang, Lei, additional, Kleist, Christian, additional, Opelz, Gerhard, additional, Süsal, Caner, additional, Ponath, Gerald, additional, Aly, Mostafa, additional, Alvarez, Cristiam M., additional, Kälble, Florian, additional, Speer, Claudius, additional, Benning, Louise, additional, Nusshag, Christian, additional, Pego da Silva, Luiza, additional, Sommerer, Claudia, additional, Hückelhoven-Krauss, Angela, additional, Czock, David, additional, Mehrabi, Arianeb, additional, Schwab, Constantin, additional, Waldherr, Rüdiger, additional, Schnitzler, Paul, additional, Merle, Uta, additional, Tran, Thuong Hien, additional, Scherer, Sabine, additional, Böhmig, Georg A., additional, Müller-Tidow, Carsten, additional, Reiser, Jochen, additional, Zeier, Martin, additional, Schmitt, Michael, additional, Terness, Peter, additional, Schmitt, Anita, additional, and Daniel, Volker, additional

Published
2022
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25. Humorale Immunantwort von Patienten mit ANCA-assoziierter Vaskulitis nach SARS-CoV-2 Impfung

Author

Töllner, Maximilian, Speer, Claudius, Benning, Louise, Schnitzler, Paul, Bartenschlager, Ralf, Schmitt, Wilhelm, Bergner, Raoul, Lorenz, Hanns-Martin, and Schaier, Matthias

Subjects
Medicine and health
Abstract

Einleitung: Immunsupprimierte haben ein erhöhtes Risiko für Infektionen und sprechen zusätzlich schlechter auf Impfungen an. Angesichts der COVID-19-Pandemie sind diese Patienten insbesondere durch Varianten mit partiellem Immune Escape wie die B.1.617.2 (delta) Variante gefährdet. [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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26. Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid

Author

Benning, Louise, primary, Morath, Christian, additional, Kühn, Tessa, additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Beimler, Jörg, additional, Buylaert, Mirabel, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reineke, Marvin, additional, Töllner, Maximilian, additional, Schaier, Matthias, additional, Klein, Katrin, additional, Blank, Antje, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Bartenschlager, Ralf, additional, Tran, Thuong Hien, additional, and Speer, Claudius, additional

Published
2022
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27. Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Reineke, Marvin; Beimler, Jorg; Buylaert, Mirabel; Nusshag, Christian; Kaelble, Florian; Reichel, Paula; Toellner, Maximilian; Schaier, Matthias; Klein, Katrin; Benes, Vladimir; Rausch, Tobias; Rieger, Susanne; Stich, Maximilian; Toenshoff, Burkhard; Weidner, Niklas; Schnitzler, Paul; Zeier, Martin; Tran, Thuong Hien; Bartenschlager, Ralf; Speer, Claudius, Koç University Hospital, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Reineke, Marvin; Beimler, Jorg; Buylaert, Mirabel; Nusshag, Christian; Kaelble, Florian; Reichel, Paula; Toellner, Maximilian; Schaier, Matthias; Klein, Katrin; Benes, Vladimir; Rausch, Tobias; Rieger, Susanne; Stich, Maximilian; Toenshoff, Burkhard; Weidner, Niklas; Schnitzler, Paul; Zeier, Martin; Tran, Thuong Hien; Bartenschlager, Ralf; Speer, Claudius, Koç University Hospital, and School of Medicine

Abstract

Seroconversion after COVID-19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age-matched healthy controls. In addition, vaccine-induced neutralization of SARS-CoV-2 wild-type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live-virus assay. After a third vaccine dose, anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine-induced cross-neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti-S1 IgG, surrogate neutralizing, and/or anti-RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all)., Dietmar Hopp Stiftung; Heidelberg Faculty of Medicine Rahel Goitein-Straus Program; Heidelberg Faculty of Medicine Physician Scientist Program; German Federal Research Network Applied Surveillance and Testing (BFAST); Network University Medicine; Helmholtz Association Initiative and Networking Fund Project Virological and Immunological Determinants of COVID-19 Pathogenesis

Published
2022

28. Impaired neutralizing antibody activity against B.1.617.2 (delta) after anti-SARS-CoV-2 vaccination in patients receiving anti-CD20 therapy

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Töllner, Maximilian; Speer, Claudiusa; Benning, Louise; Bartenschlager, Marie;Nusshag, Christian; Morath, Christian; Zeier, Martin; Schnitzler, Paul; Schmitt, Wilhelm; Bergner, Raoul; Bartenschlager, Ralf; Lorenz, Hanns-Martin; Schaier, Matthiasa, Koç University Hospital, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Töllner, Maximilian; Speer, Claudiusa; Benning, Louise; Bartenschlager, Marie;Nusshag, Christian; Morath, Christian; Zeier, Martin; Schnitzler, Paul; Schmitt, Wilhelm; Bergner, Raoul; Bartenschlager, Ralf; Lorenz, Hanns-Martin; Schaier, Matthiasa, Koç University Hospital, and School of Medicine

Abstract

Background: to characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19+ peripheral B-cells were quantified using flow cytometry. Results: after second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID50 of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all p < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19+ cell proportion ? 1% had detectable neutralizing antibodies. Conclusion: our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8–12 months after the last Rituximab treatment for sufficient humoral responses., Dietmar Hopp Stiftung; Heidelberg Faculty of Medicine Rahel Goitein-Strauss Program; Heidelberg Faculty of Medicine Physician Scientist Program; German Federal Research Network Applied Surveillance and Testing (BFAST); Network University Medicine; Virological and Immunological Determinants of COVID-19 Pathogenesis; Helmholtz Association Initiative and Networking Fund Project

Published
2022

29. Neutralization of SARS-CoV-2 variants of concern in kidney transplant recipients after standard COVID-19 vaccination

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Bartenschlager, Marie; Nusshag, Christian; Kalble, Florian; Buylaert, Mirabel; Schaier, Matthias; Beimler, Jorg; Klein, Katrin; Grenz, Julia; Reichel, Paula; Hidmark, Asa; Ponath, Gerald; Tollner, Maximilian; Reineke, Marvin; Rieger, Susanne; Tonshoff, Burkhard; Schnitzler, Paul; Zeier, Martin; Bartenschlager, Ralf; Speer, Claudius, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Benning, Louise; Morath, Christian; Bartenschlager, Marie; Nusshag, Christian; Kalble, Florian; Buylaert, Mirabel; Schaier, Matthias; Beimler, Jorg; Klein, Katrin; Grenz, Julia; Reichel, Paula; Hidmark, Asa; Ponath, Gerald; Tollner, Maximilian; Reineke, Marvin; Rieger, Susanne; Tonshoff, Burkhard; Schnitzler, Paul; Zeier, Martin; Bartenschlager, Ralf; Speer, Claudius, and School of Medicine

Abstract

Background and objectives: antibody response after severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 ( d), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients. Design, setting, participants, and measurements: in this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 ( a), B.1.351 ( b), and B.1.617.2 ( d) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls. Results: kidney transplant recipients had significantly lower seroconversion rates compared with healthy controls. After the second vaccination, antispike 1, antireceptor-binding domain, and surrogate neutralizing antibodies were detectable in 30%, 27%, and 24% of kidney transplant recipients, respectively. This compares with 100%, 96%, and 100% in healthy controls, respectively (P,0.001). Neutralization against B.1.1.7 was detectable in all kidney transplant recipients with seroconversion, with a median serum dilution that reduces infection of cells by 50% of 80 (interquartile range, 80-320). In contrast, only 23 of 36 (64%) and 24 of 36 (67%) kidney transplant recipients showed neutralization against B.1.351 and B.1.617.2, respectively, with median serum dilutions that reduce infection of cells by 50% of 20 (interquartile range, 0-40) and 20 (interquartile range, 0-40), respectively. Neutralization against different variants was signif, Dietmar Hopp Stiftung; German Federal Research Network Applied Surveillance and Testing; Network University Medicine; fightCOVID@DKFZ Initiative; Helmholtz Association Initiative and Networking Fund Project Virological and Immunological Determinants of COVID-19 Pathogenesis; Lessons to Get Prepared for Future Pandemics; Heidelberg Faculty of Medicine Rahel Goitein-Strauss Program; Heidelberg Faculty of Medicine Physician Scientist Program

Published
2022

31. Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy

Author

Töllner, Maximilian, primary, Speer, Claudius, additional, Benning, Louise, additional, Bartenschlager, Marie, additional, Nusshag, Christian, additional, Morath, Christian, additional, Zeier, Martin, additional, Süsal, Caner, additional, Schnitzler, Paul, additional, Schmitt, Wilhelm, additional, Bergner, Raoul, additional, Bartenschlager, Ralf, additional, Lorenz, Hanns-Martin, additional, and Schaier, Matthias, additional

Published
2022
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32. Neutralizing Antibody Activity Against the B.1.617.2 (delta) Variant Before and After a Third BNT162b2 Vaccine Dose in Hemodialysis Patients

Author

Benning, Louise, primary, Klein, Katrin, additional, Morath, Christian, additional, Bartenschlager, Marie, additional, Kim, Heeyoung, additional, Buylaert, Mirabel, additional, Reineke, Marvin, additional, Töllner, Maximilian, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reichel, Paula, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Bartenschlager, Ralf, additional, Schaier, Matthias, additional, and Speer, Claudius, additional

Published
2022
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34. Humoral Responses and Chronic GVHD Exacerbation after COVID-19 Vaccination Post Allogeneic Stem Cell Transplantation

Author

Pabst, Caroline, primary, Benning, Louise, additional, Liebers, Nora, additional, Janssen, Maike, additional, Caille, Leandra, additional, Speer, Claudius, additional, He, Lixiazi, additional, Schubert, Maria-Luisa, additional, Simons, Laura, additional, Hegenbart, Ute, additional, Schönland, Stefan, additional, Radujkovic, Aleksandar, additional, Schmitt, Michael, additional, Schnitzler, Paul, additional, Müller-Tidow, Carsten, additional, Dietrich, Sascha, additional, Dreger, Peter, additional, and Luft, Thomas, additional

Published
2022
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35. Third COVID-19 vaccine dose with BNT162b2 in patients with ANCA-associated vasculitis

Author

Speer, Claudius, primary, Töllner, Maximilian, additional, Benning, Louise, additional, Klein, Katrin, additional, Bartenschlager, Marie, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reichel, Paula, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Morath, Christian, additional, Schmitt, Wilhelm H, additional, Bergner, Raoul, additional, Bartenschlager, Ralf, additional, and Schaier, Matthias, additional

Published
2022
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36. Neutralization of SARS-CoV-2 Variants of Concern in Kidney Transplant Recipients after Standard COVID-19 Vaccination

Author

Benning, Louise, primary, Morath, Christian, additional, Bartenschlager, Marie, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Buylaert, Mirabel, additional, Schaier, Matthias, additional, Beimler, Jörg, additional, Klein, Katrin, additional, Grenz, Julia, additional, Reichel, Paula, additional, Hidmark, Asa, additional, Ponath, Gerald, additional, Töllner, Maximilian, additional, Reineke, Marvin, additional, Rieger, Susanne, additional, Tönshoff, Burkhard, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Bartenschlager, Ralf, additional, and Speer, Claudius, additional

Published
2022
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37. Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption

Author

Kälble, Florian, primary, Süsal, Caner, additional, Pego da Silva, Luiza, additional, Speer, Claudius, additional, Benning, Louise, additional, Nusshag, Christian, additional, Pham, Lien, additional, Tran, Hien, additional, Schaier, Matthias, additional, Sommerer, Claudia, additional, Beimler, Jörg, additional, Mehrabi, Arianeb, additional, Zeier, Martin, additional, and Morath, Christian, additional

Published
2021
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39. Longitudinal Humoral Responses after COVID-19 Vaccination in Peritoneal and Hemodialysis Patients over Twelve Weeks

Author

Speer, Claudius, primary, Schaier, Matthias, additional, Nusshag, Christian, additional, Töllner, Maximilian, additional, Buylaert, Mirabel, additional, Kälble, Florian, additional, Reichel, Paula, additional, Grenz, Julia, additional, Süsal, Caner, additional, Zeier, Martin, additional, Schnitzler, Paul, additional, Morath, Christian, additional, Klein, Katrin, additional, and Benning, Louise, additional

Published
2021
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40. Humoral Responses to Single-Dose BNT162b2 mRNA Vaccination in Dialysis Patients Previously Infected With SARS-CoV-2

Author

Speer, Claudius, primary, Morath, Christian, additional, Töllner, Maximilian, additional, Buylaert, Mirabel, additional, Göth, Daniel, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Schaier, Matthias, additional, Grenz, Julia, additional, Kreysing, Martin, additional, Reichel, Paula, additional, Hidmark, Asa, additional, Ponath, Gerald, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Klein, Katrin, additional, and Benning, Louise, additional

Published
2021
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41. Heterologous ChAdOx1 nCoV-19/BNT162b2 Prime-Boost Vaccination Induces Strong Humoral Responses among Health Care Workers

Author

Benning, Louise, primary, Töllner, Maximilian, additional, Hidmark, Asa, additional, Schaier, Matthias, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Reichel, Paula, additional, Buylaert, Mirabel, additional, Grenz, Julia, additional, Ponath, Gerald, additional, Klein, Katrin, additional, Zeier, Martin, additional, Süsal, Caner, additional, Schnitzler, Paul, additional, Morath, Christian, additional, and Speer, Claudius, additional

Published
2021
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42. Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b2

Author

Speer, Claudius, primary, Göth, Daniel, additional, Benning, Louise, additional, Buylaert, Mirabel, additional, Schaier, Matthias, additional, Grenz, Julia, additional, Nusshag, Christian, additional, Kälble, Florian, additional, Kreysing, Martin, additional, Reichel, Paula, additional, Töllner, Maximilian, additional, Hidmark, Asa, additional, Ponath, Gerald, additional, Schnitzler, Paul, additional, Zeier, Martin, additional, Süsal, Caner, additional, Morath, Christian, additional, and Klein, Katrin, additional

Published
2021
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43. Living donor kidney transplantation in patients with donor-specific HLA antibodies after desensitization with immunoadsorption

Author

Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Kalble, Florian; Pego da Silva, Luiza; Speer, Claudius; Benning, Louise; Nusshag, Christian; Pham, Lien; Tran, Hien; Schaier, Matthias; Sommerer, Claudia; Beimler, Jörg; Mehrabi, Arianeb; Zeier, Martin; Morath, Christian, School of Medicine, Süsal, Caner (ORCID 0000-0003-2521-8201 & YÖK ID 351800), Kalble, Florian; Pego da Silva, Luiza; Speer, Claudius; Benning, Louise; Nusshag, Christian; Pham, Lien; Tran, Hien; Schaier, Matthias; Sommerer, Claudia; Beimler, Jörg; Mehrabi, Arianeb; Zeier, Martin; Morath, Christian, and School of Medicine

Abstract

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent, Dietmar Hopp Stiftung

Published
2021

44. Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients

Author

Morath, Christian, Schaier, Matthias, Ibrahim, Eman, Wang, Lei, Kleist, Christian, Opelz, Gerhard, Süsal, Caner, Ponath, Gerald, Aly, Mostafa, Alvarez, Cristiam M., Kälble, Florian, Speer, Claudius, Benning, Louise, Nusshag, Christian, Pego da Silva, Luiza, Sommerer, Claudia, Hückelhoven-Krauss, Angela, Czock, David, Mehrabi, Arianeb, Schwab, Constantin, Waldherr, Rüdiger, Schnitzler, Paul, Merle, Uta, Tran, Thuong Hien, Scherer, Sabine, Böhmig, Georg A., Müller-Tidow, Carsten, Reiser, Jochen, Zeier, Martin, Schmitt, Michael, Terness, Peter, Schmitt, Anita, and Daniel, Volker

Abstract

In previous work, the authors demonstrated that kidney transplant recipients developed donor-specific unresponsiveness when they were given a pretransplant infusion of modified donor-derived PBMCs. In this study, they provide evidence that the immunosuppressive properties of these cells persist and the donor-specific unresponsiveness is long-lasting. In the four patients who received the highest dose of the modified immune cells, administration of these cells was associated with a striking increase in IL-10–producing regulatory B lymphocytes and evidence of the consensus gene expression signature of operational tolerance. In vitro, donor-specific unresponsiveness was abolished after B lymphocyte depletion, suggesting a direct pathophysiologic role for regulatory B lymphocytes. These findings support the notion that modified donor-derived PBMCs may be useful in kidney transplantation, but this approach requires further validation and rigorous controlled randomized studies.

Published
2023
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45. Right To Regenerate

Author

Benning, Louise

Subjects
Land use -- Laws, regulations and rules -- United Kingdom, Local government -- Powers and duties, Government regulation, Business, international
Abstract

The Ministry of Housing, Communities and Local Government (MHCLG) recently announced a new 'Right to Regenerate' consultation which will allow the public to require councils and the public sector to [...]

Published
2021

46. Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease

Author

Benning, Louise, Robinson, Samuel, Follo, Marie, Heger, Lukas Andreas, Stallmann, Daniela, Duerschmied, Daniel, Bode, Christoph, Ahrens, Ingo, Hortmann, Marcus, Benning, Louise, Robinson, Samuel, Follo, Marie, Heger, Lukas Andreas, Stallmann, Daniela, Duerschmied, Daniel, Bode, Christoph, Ahrens, Ingo, and Hortmann, Marcus

Abstract

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released from the cardiovascular cells into the circulation. Circulating miRNAs are highly stable and can be quantified. The quantitative expression of specific miRNAs can be linked to the pathology, and some miRNAs show high tissue and disease specificity. Finding novel biomarkers for cardiovascular diseases is of importance for medical research. Quite recently, digital polymerase chain reaction (dPCR) has been invented. dPCR, combined with fluorescent hydrolysis probes, enables specific direct absolute quantification. dPCR exhibits superior technical qualities, including a low variability, high linearity, and high sensitivity compared to the quantitative polymerase chain reaction (qPCR). Thus, dPCR is a more accurate and reproducible method for directly quantifying miRNAs, particularly for the use in large multi-center cardiovascular clinical trials. In this publication, we describe how to effectively perform digital PCR in order to assess the absolute copy number in serum samples.

Published
2018

49. Court Backs Government Plans To Exempt Small Sites From Affordable Homes Obligations

Author

Benning, Louise

Subjects
Housing -- Laws, regulations and rules -- Statistics, Government regulation, Business, international
Abstract

The government has won a legal challenge against a High Court ruling that quashed a national planning policy intended to exempt small sites from affordable housing obligations. The Court of [...]

Published
2016

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