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Pattonieri EF, Gregorini M, Grignano MA, Islami T, D’Ambrosio G, Ardissino G, Rampino T. Atypical Hemolytic Uremic Syndrome Associated with BNT162b2 mRNA COVID-19 Vaccine in a Kidney Transplant Recipient: A Case Report and Literature Review. Infect Dis Rep 2025; 17:14. [PMID: 39997466 PMCID: PMC11855336 DOI: 10.3390/idr17010014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/30/2024] [Accepted: 11/07/2024] [Indexed: 02/26/2025] Open
Abstract
Case Report: We report a case of a 37-year-old female with kidney transplant, who was admitted at our hospital due to worsening renal function, nephrotic proteinuria, and anemia developed 21 days after the second dose of BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Laboratory tests revealed hemolytic anemia, thrombocytopenia, and acute kidney injury. Given the clinical picture of Thrombotic Micro-angiopathy (TMA) and severe renal impairment, plasma exchange (PEX) and dialysis were immediately started. Laboratory workup showed low C3 and C4 levels, normal activity of ADAMTS13, and the absence of anti-factor H antibodies. Molecular biology investigations revealed a heterozygous variant in exon 22 (SCR20) of the CFH gene (c.3628C>T; p.Arg1210Cys) described as an atypical Hemolytic Uremic Syndrome (aHUS) causative mutation. Our patient completed two sessions of PEX followed by eculizumab treatment with hematological improvement but no recovery of renal function. This is the first reported case of aHUS triggered by SARS-CoV-2 vaccination in a kidney transplant patient without recovery of renal function. Conclusion: Although rare, clinicians should be aware of possible nephrological complications that may appear after vaccination.
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Affiliation(s)
- Eleonora Francesca Pattonieri
- Unit of Nephrology, Dialysis and Transplants, Fondazione I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy; (E.F.P.); (T.I.); (T.R.)
| | - Marilena Gregorini
- Unit of Nephrology, Dialysis and Transplants, Fondazione I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy; (E.F.P.); (T.I.); (T.R.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Maria Antonietta Grignano
- Unit of Nephrology, Dialysis and Transplants, Fondazione I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy; (E.F.P.); (T.I.); (T.R.)
| | - Tefik Islami
- Unit of Nephrology, Dialysis and Transplants, Fondazione I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy; (E.F.P.); (T.I.); (T.R.)
| | - Gioacchino D’Ambrosio
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Gianluigi Ardissino
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20162 Milano, Italy;
| | - Teresa Rampino
- Unit of Nephrology, Dialysis and Transplants, Fondazione I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy; (E.F.P.); (T.I.); (T.R.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
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Çerçi Alkaç B, Soyöz M, Pehlivan M, Kılıçaslan Ayna T, Tatar E, Karahan Çöven Hİ, Tanrısev M, Pirim İ. Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels. Biochem Genet 2025; 63:526-539. [PMID: 38467886 DOI: 10.1007/s10528-024-10723-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 01/28/2024] [Indexed: 03/13/2024]
Abstract
CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is an immune regulator molecule that is expressed on a variety of immune cells, including CD4+ and CD8+ T cells. After realizing the significance of this regulator molecule, researchers began to concentrate on its activation or inhibition in cancer. Even though there have been some studies on organ transplantation and autoimmunity, the role of the CTLA-4 molecule in renal transplantation has not been demonstrated. The goal of this study was to see how CTLA-4 gene expression and serum sCTLA-4 levels affected renal transplant patients. Peripheral blood samples were collected before and 1-3 months after renal transplantation from 29 recipients. CD8+ T lymphocytes were separated using magnetic beads and purity of the cells controlled by Flow cytometry. CTLA-4 mRNA levels were determined by Real-Time PCR while serum sCTLA-4 levels were assessed by ELISA. 55% of the patient had decreased level of CTLA-4 mRNA after transplantation when compared to pre-transplantation levels. Moreover 61% of the patient had lower serum sCTLA-4 levels after transplantation. sCTLA-4 levels were decreased 11% of the patients with rejection episode after transplantation when compared to stabile patients (5%). Kidney rejection is a complicated process influenced by numerous unknown factors. Several parameters should be evaluated together to precise rejection episodes or graft dysfunctions. Further research focused on the other immune checkpoint regulator molecules could give an opportunity to have an idea about the effect of these molecules on renal transplantation.
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Affiliation(s)
- Burcu Çerçi Alkaç
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Türkiye.
| | - Mustafa Soyöz
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Türkiye
| | - Melek Pehlivan
- Vocational School of Health Services, Izmir Katip Celebi University, Izmir, Türkiye
| | - Tülay Kılıçaslan Ayna
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Türkiye
| | - Erhan Tatar
- Department of Nephrology, Bozyaka Training and Research Hospital, University of Health Science, Izmir, Türkiye
| | - H İlayhan Karahan Çöven
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Türkiye
| | - Mehmet Tanrısev
- Department of Nephrology, Tepecik Training and Research Hospital, University of Health Science, Izmir, Türkiye
| | - İbrahim Pirim
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Türkiye
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Parlakpinar H, Gunata M. Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs. Immunopharmacol Immunotoxicol 2021; 43:651-665. [PMID: 34415233 DOI: 10.1080/08923973.2021.1966033] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard.Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.
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Affiliation(s)
- Hakan Parlakpinar
- Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Mehmet Gunata
- Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey
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4
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Taddio MF, Castro Jaramillo CA, Runge P, Blanc A, Keller C, Talip Z, Béhé M, van der Meulen NP, Halin C, Schibli R, Krämer SD. In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET. Mol Imaging Biol 2021; 23:196-207. [PMID: 32989622 PMCID: PMC7910267 DOI: 10.1007/s11307-020-01543-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 08/11/2020] [Accepted: 09/10/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. PROCEDURES Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. RESULTS The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. CONCLUSIONS CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time.
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Affiliation(s)
- Marco F Taddio
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
| | - Claudia A Castro Jaramillo
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland
| | - Peter Runge
- Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
| | - Alain Blanc
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland
| | - Claudia Keller
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland
| | - Zeynep Talip
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland
| | - Martin Béhé
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland
| | - Nicholas P van der Meulen
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland
- Laboratory of Radiochemistry, Paul Scherrer Institute (PSI), Villigen, Switzerland
| | - Cornelia Halin
- Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
| | - Roger Schibli
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland
| | - Stefanie D Krämer
- Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
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Spicer P, Runkel L. Costimulatory pathway targets for autoimmune and inflammatory conditions: clinical successes, failures, and hope for the future. Expert Opin Investig Drugs 2019; 28:99-106. [DOI: 10.1080/13543784.2019.1557146] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation. J Immunol Res 2019; 2019:7452019. [PMID: 30729139 PMCID: PMC6341262 DOI: 10.1155/2019/7452019] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 10/16/2018] [Accepted: 11/12/2018] [Indexed: 01/08/2023] Open
Abstract
Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9 ± 2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28− lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28− population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.
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Gregorini M, Martinelli V, Ticozzelli E, Canevari M, Fasoli G, Pattonieri EF, Erasmi F, Valente M, Esposito P, Contardi A, Grignano MA, Pietrabissa A, Abelli M, Rampino T. Living Kidney Donation Is Recipient Age Sensitive and Has a High Rate of Donor Organ Disqualifications. Transplant Proc 2019; 51:120-123. [PMID: 30655157 DOI: 10.1016/j.transproceed.2018.03.136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/05/2018] [Accepted: 03/15/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation. METHODS This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017. RESULTS During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P < .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%). CONCLUSION LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.
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Affiliation(s)
- M Gregorini
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - V Martinelli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - E Ticozzelli
- Unit of General Surgery 2, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
| | - M Canevari
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - G Fasoli
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - E F Pattonieri
- Experimental Medicine Doctorate, University of Pavia, Pavia, Italy
| | - F Erasmi
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - M Valente
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - P Esposito
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - A Contardi
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - M A Grignano
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - A Pietrabissa
- Unit of General Surgery 2, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - M Abelli
- Renal Transplant Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - T Rampino
- Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
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8
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Doublier S, Zennaro C, Musante L, Spatola T, Candiano G, Bruschi M, Besso L, Cedrino M, Carraro M, Ghiggeri GM, Camussi G, Lupia E. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS. PLoS One 2017; 12:e0188045. [PMID: 29155846 PMCID: PMC5695800 DOI: 10.1371/journal.pone.0188045] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 10/31/2017] [Indexed: 12/17/2022] Open
Abstract
CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.
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Affiliation(s)
- Sophie Doublier
- Department of Oncology, University of Turin, Turin, Italy
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Cristina Zennaro
- Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy
| | - Luca Musante
- Nephrology, Dialysis, Transplantation and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy
| | - Tiziana Spatola
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giovanni Candiano
- Nephrology, Dialysis, Transplantation and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy
| | - Maurizio Bruschi
- Nephrology, Dialysis, Transplantation and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy
| | - Luca Besso
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Massimo Cedrino
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Michele Carraro
- Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy
| | - Gian Marco Ghiggeri
- Nephrology, Dialysis, Transplantation and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy
| | - Giovanni Camussi
- Department of Medical Sciences, University of Turin, Turin, Italy
- * E-mail: (EL); (GC)
| | - Enrico Lupia
- Department of Medical Sciences, University of Turin, Turin, Italy
- * E-mail: (EL); (GC)
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Betjes MGH. Clinical consequences of circulating CD28-negative T cells for solid organ transplantation. Transpl Int 2015; 29:274-84. [DOI: 10.1111/tri.12658] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Revised: 07/06/2015] [Accepted: 08/11/2015] [Indexed: 12/14/2022]
Affiliation(s)
- Michiel G. H. Betjes
- Department of Nephrology and Transplantation; Erasmus Medical Center; Rotterdam the Netherlands
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Esposito P, Rampino T, Canton AD. Costimulatory blockade: A novel approach to the treatment of glomerular disease? World J Methodol 2015; 5:20-25. [PMID: 26140268 PMCID: PMC4482818 DOI: 10.5662/wjm.v5.i2.20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 04/01/2015] [Accepted: 05/16/2015] [Indexed: 02/06/2023] Open
Abstract
Costimulatory pathways (Cluster of differentiation 28, tumor necrosis factor-related, adhesion and T Cell Ig- and mucin-domain molecules) regulating the interactions between receptors on the T cells and their ligands expressed on several cell types, have a key role in controlling many immunological and non immunological processes. Indeed, accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions, such as allograft rejection, atherosclerosis, rheumatoid arthritis, psoriasis and renal diseases, including glomerulonephritis. Primary or secondary (i.e., associated with infections, drugs or systemic diseases, such as systemic lupus erythematosus, diabetes, etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms. Since costimulatory molecules, in particular CD80 and CD40, have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis, costimulation has been thought as a new therapeutic target for patients with glomerular diseases. However, although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases, clinical trials reported contrasting results. So, at this moment, there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis. Here, we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach.
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11
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Clark EA. A Short History of the B-Cell-Associated Surface Molecule CD40. Front Immunol 2014; 5:472. [PMID: 25324844 PMCID: PMC4179537 DOI: 10.3389/fimmu.2014.00472] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 09/14/2014] [Indexed: 12/28/2022] Open
Abstract
This perspective traces developments using monoclonal antibody technology that led to the discovery of CD40, a receptor that on B cells mediates “T cell help” and on dendritic cells helps to program CD8 T cell responses. I discuss some things that we got right during the path of discovery and some things we missed. Immunotherapies that block or stimulate the CD40 pathway hold great promise for treatment of autoimmune diseases and cancers.
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Affiliation(s)
- Edward A Clark
- Department of Immunology, University of Washington , Seattle, WA , USA
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