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Book ; Online: DataSheet_1_Immunosuppressive Drugs and COVID-19

Tessa S. Schoot / Angèle P. M. Kerckhoffs / Luuk B. Hilbrands / Rob J. van Marum

A Review.pdf

2020

Abstract: Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive ...

Abstract	Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the “cytokine storm”) can cause ARDS, multiorgan failure and mortality. Aim To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) Methods The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group. Results and Conclusion Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro. Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo. There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.
Keywords	Pharmacology ; Basic Pharmacology ; Clinical Pharmacology and Therapeutics ; Clinical Pharmacy and Pharmacy Practice ; Pharmaceutical Sciences ; Pharmacogenomics ; Toxicology (incl. Clinical Toxicology) ; Pharmacology and Pharmaceutical Sciences not elsewhere classified ; COVID-19 ; SARS-CoV-2 ; coronavirus ; immunosuppressive drugs ; corticosteroids ; mycophenolic acid ; calcineurin inhibitors ; mTOR inhibitors ; covid19
Subject code	610
Publishing date	2020-08-28T14:07:04Z
Publishing country	uk
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunosuppressive Drugs and COVID-19

Tessa S. Schoot / Angèle P. M. Kerckhoffs / Luuk B. Hilbrands / Rob J. van Marum

Frontiers in Pharmacology, Vol

A Review

2020 Volume 11

Abstract: BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive ... ...

Abstract	BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the “cytokine storm”) can cause ARDS, multiorgan failure and mortality.AimTo summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)MethodsThe study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group.Results and ConclusionSixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro. Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo. There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.
Keywords	COVID-19 ; SARS-CoV-2 ; coronavirus ; immunosuppressive drugs ; corticosteroids ; mycophenolic acid ; Therapeutics. Pharmacology ; RM1-950 ; covid19
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

Kim L. W. Bunthof / Linda Al‐Hassany / Gizal Nakshbandi / Dennis A. Hesselink / Ron H. N. vanSchaik / Marc A. G. J. ten Dam / Marije C. Baas / Luuk B. Hilbrands / Teun vanGelder

Clinical and Translational Science, Vol 15, Iss 4, Pp 930-

2022 Volume 941

Abstract: Abstract A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long‐term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients ...

Abstract	Abstract A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long‐term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients from immediate‐release (IR)‐tacrolimus to either extended‐release (ER)‐tacrolimus or LifeCyclePharma (LCP)‐tacrolimus. In this randomized, prospective, open‐label, cross‐over trial, adult kidney transplant recipients on a stable immunosuppressive regimen, including IR‐tacrolimus, were randomized for conversion to ER‐tacrolimus or LCP‐tacrolimus, and for the order in which IR‐tacrolimus and the once‐daily formulations were taken. Patients were followed 6 months for each formulation, with monthly tacrolimus predose concentration assessments to calculate the IPV. The IPV was defined as the coefficient of variation (%) of dose corrected predose concentrations. Ninety‐two patients were included for analysis of the primary outcome. No significant differences between the IPV of IR‐tacrolimus (16.6%) and the combined once‐daily formulations (18.3%) were observed (% difference +1.7%, 95% confidence interval [CI] −1.1% to ‒4.5%, p = 0.24). The IPV of LCP‐tacrolimus (20.1%) was not significantly different from the IPV of ER‐tacrolimus (16.5%, % difference +3.6%, 95% CI −0.1% to 7.3%, p = 0.06). In conclusion, the IPV did not decrease after switching from IR‐tacrolimus to either ER‐tacrolimus or LCP‐tacrolimus. These results provide no arguments to switch kidney transplant recipients from twice‐daily (IR) tacrolimus formulations to once‐daily (modified‐release) tacrolimus formulations when the aim is to lower the IPV.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: E-HEalth treatment in Long-term Dialysis (E-HELD)

Judith Tommel / Andrea W. M. Evers / Henk W. van Hamersvelt / Sandra van Dijk / Niels H. Chavannes / Lieke Wirken / Luuk B. Hilbrands / Henriët van Middendorp

Trials, Vol 23, Iss 1, Pp 1-

study protocol for a multicenter randomized controlled trial evaluating personalized Internet-based cognitive-behavioral therapy in dialysis patients

2022 Volume 20

Abstract: Abstract Background Kidney failure and dialysis treatment have a large impact on a patient’s life. Patients experience numerous, complex symptoms and usually have multiple comorbid conditions. Despite the multitude of problems, patients often have ... ...

Abstract	Abstract Background Kidney failure and dialysis treatment have a large impact on a patient’s life. Patients experience numerous, complex symptoms and usually have multiple comorbid conditions. Despite the multitude of problems, patients often have priorities for improvement of specific aspects of their functioning, which would be helpful for clinicians to become informed of. This highlights a clear need for patient-centered care in this particular patient group, with routine screening as a vital element to timely recognize symptoms and tailored treatment to match individual patients’ needs and priorities. By also providing feedback on patient’s screening results to the patient itself, the patient is empowered to actively take control in one’s mostly uncontrollable disease process. The current paper describes the study design of a multicenter randomized controlled trial evaluating the effectiveness of the “E-HEealth treatment in Long-term Dialysis” (E-HELD) intervention. This therapist-guided Internet-based cognitive-behavioral therapy (ICBT) intervention is focused on and personalized to the myriad of problems that dialysis patients experience and prioritize. Methods After a screening procedure on adjustment problems, 130 eligible dialysis patients will be randomized to care as usual or the E-HELD intervention. Patients will complete questionnaires on distress (primary outcome measure), several domains of functioning (e.g., physical, psychological, social), potential predictors and mediators of treatment success, and the cost-effectiveness of the intervention, at baseline, 6-month follow-up, and 12-month follow-up. In addition, to take account of the personalized character of the intervention, the Personalized Priority and Progress Questionnaire (PPPQ) will be administered which is a personalized instrument to identify, prioritize, and monitor individual problems over time. Discussion The present study design will provide insight in the effectiveness of tailored ICBT in patients with kidney failure who are ...
Keywords	Kidney failure ; Dialysis ; Internet-based cognitive-behavioral therapy (ICBT) ; Screening ; Patient-centered care ; Personalized medicine ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application

Milos Mihajlovic / Lambertus P. van den Heuvel / Joost G. Hoenderop / Jitske Jansen / Martijn J. Wilmer / Annemarie J. F. Westheim / Wil A. Allebes / Dimitrios Stamatialis / Luuk B. Hilbrands / Rosalinde Masereeuw

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 14

Abstract: Abstract Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the ... ...

Abstract	Abstract Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α). A lack of direct immunogenic effect of ciPTEC was shown in co-culture experiments with peripheral blood mononuclear cells (PBMC), after appropriate stimulation of ciPTEC. Tight epithelial cell monolayer formation on polyethersulfone flat membranes was confirmed by zonula occludens-1 (ZO-1) expression in the ciPTEC tight junctions, and by restricted inulin-FITC diffusion. Co-culture with (activated) PBMC did not jeopardize the transepithelial barrier function of ciPTEC. In conclusion, the absence of allostimulatory effects and the stability of ciPTEC monolayers show that these unique cells could represent a safe option for BAK engineering application.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2017-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions

Milos Mihajlovic / Michele Fedecostante / Miriam J. Oost / Sonja K. P. Steenhuis / Eef G. W. M. Lentjes / Inge Maitimu-Smeele / Manoe J. Janssen / Luuk B. Hilbrands / Rosalinde Masereeuw

International Journal of Molecular Sciences, Vol 18, Iss 12, p

2017 Volume 2531

Abstract: As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an ... ...

Abstract	As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25-hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.
Keywords	bioartificial kidney ; conditionally immortalized proximal tubule cells ; chronic kidney disease ; end-stage renal disease ; vitamin D ; uremic toxins ; epithelial barrier ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury.

Nuria Maicas / Johan van der Vlag / Janin Bublitz / Sandrine Florquin / Marinka Bakker-van Bebber / Charles A Dinarello / Vivienne Verweij / Roos Masereeuw / Leo A Joosten / Luuk B Hilbrands

PLoS ONE, Vol 12, Iss 2, p e

2017 Volume 0168981

Abstract: Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) ... ...

Abstract	Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis.

Jürgen Dieker / Jo H Berden / Marinka Bakker / Jean-Paul Briand / Sylviane Muller / Reinhard Voll / Christopher Sjöwall / Martin Herrmann / Luuk B Hilbrands / Johan van der Vlag

PLoS ONE, Vol 11, Iss 10, p e

2016 Volume 0165373

Abstract: Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs ... ...

Abstract	Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adherence to preventive measures after SARS-CoV-2 vaccination and after awareness of antibody response in kidney transplant recipients in the Netherlands

Sophie C. Frölke / Pim Bouwmans / A. Lianne Messchendorp / Johanna P.M. Vervoort / Alferso C. Abrahams / Aiko P.J. de Vries / Pythia T. Nieuwkerk / Marc H. Hemmelder / Ron T. Gansevoort / Luuk B. Hilbrands / Marlies E.J. Reinders / Jan-Stephan F. Sanders / Frederike J. Bemelman / Suzanne E. Geerlings / C. Imhof / C. Idzinga / C. Siegert / C.C. Baan / C.J.A.M. Konings /

C. van Kessel / D. van Baarle / D.A. Diavatopoulos / D. Standaar / E. ten Hoope / E. Til / E.B.M. Remmerswaal / F. van der Klis / H.R. Fritsen / I. Stijnman / J.N. Brinkman / J. Cheng / L. den Biggelaar / M. ten Dam / M. Steenhuis / M. Zwerink / M.H.J. Braks / M. Willems / M.L. Kho / N. Rots / P. Vart / R.G. van der Molen / R.M.A. van den Dorpel / R.S.R.K. Malaha / R.C.G. ter Meulen / T. Rispens / T. Steenvoorden / T. de Ronde / V.J.P. Peters / W.S. Konijn / W.M.T. Janssen / W.J. Bos / Y.M.R. Adema / Y. Vegting

EClinicalMedicine, Vol 62, Iss , Pp 102103- (2023)

a nationwide questionnaire studyResearch in context

2023

Abstract: Summary: Background: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and ...

Abstract	Summary: Background: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness. Methods: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (>50 ≤ 300 BAU/mL) or high-responder (>300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785). Findings: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11–4.78 and 4.22, IQR 3.67–4.67, p < 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to ...
Keywords	Kidney transplantation ; SARS-CoV-2 ; Vaccination ; Behavior ; Adherence ; Medicine (General) ; R5-920
Subject code	796
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(pos)CD25(high) T cells for immunotherapy.

Jorieke H Peters / Luuk B Hilbrands / Hans J P M Koenen / Irma Joosten

PLoS ONE, Vol 3, Iss 5, p e

2008 Volume 2233

Abstract: BACKGROUND: Regulatory T cell (Treg) based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg ... ...

Abstract	BACKGROUND: Regulatory T cell (Treg) based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(pos)CD25(high) Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2008-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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