Article
Medicine, Research & Experimental
Jan Novak, Tana Machackova, Jan Krejci, Julie Bienertova-Vasku, Ondrej Slaby
Summary: Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation is one of the last options for patients with terminal refractory heart failure. The prognosis of patients after heart transplantation is influenced by rejection and allograft vasculopathy, with monitoring requiring invasive and uncomfortable procedures. MiRNAs play a potential role in the pathophysiology of rejection and may be used in clinical practice for diagnosis and prediction of rejection occurrence.
Article
Immunology
Claire Tinel, Baptiste Lamarthee, Jasper Callemeyn, Elisabet Van Loon, Virginia Sauvaget, Lise Morin, Laila Aouni, Marion Rabant, Wilfried Gwinner, Pierre Marquet, Maarten Naesens, Dany Anglicheau
Summary: miRNAs play key roles in antibody-mediated rejection in solid-organ transplantation by regulating cellular functions, such as endothelial cells, epithelial cells, and immune cells, impacting the development of microvascular inflammation as well as renal immune response and electrolyte homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Min Young Kim, Daniel C. Brennan
Summary: Significant progress has been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) in recent decades, but effective treatment for chronic ABMR remains a challenge. Chronic ABMR has a distinct phenotype from active ABMR and is mainly caused by de novo donor specific antibodies (DSA), leading to progressive graft injury.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Qinfan Yao, Cuili Wang, Yucheng Wang, Wenyu Xiang, Yin Chen, Qin Zhou, Jianghua Chen, Hong Jiang, Dajin Chen
Summary: This study identified key differentially expressed genes (DEGs) in acute allograft rejection (AR) and found that they have the potential to be used as biomarkers for early-stage AR diagnosis. The expression of these genes can reflect the immune status of patients with AR.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Guillaume Coutance, Eva Desire, Jean-Paul Duong Van Huyen
Summary: Despite advances in immunosuppression, allograft rejection remains a significant complication after heart transplantation. The current invasive diagnostic method has limitations, thus innovative strategies are needed to improve the accuracy of diagnosis.
Article
Cardiac & Cardiovascular Systems
Palak Shah, Sean Agbor-Enoh, Pramita Bagchi, Christopher R. deFilippi, Angela Mercado, Gouqing Diao, Dave J. P. Morales, Keyur B. Shah, Samer S. Najjar, Erika Feller, Steven Hsu, Maria E. Rodrigo, Sabra C. Lewsey, Moon Kyoo Jang, Charles Marboe, Gerald J. Berry, Kiran K. Khush, Hannah A. Valantine, GRAfT Investigators
Summary: By analyzing and studying miR expression data in heart transplant patients, miR panels with high diagnostic accuracy for acute rejection can be developed, providing a new non-invasive method for clinical monitoring of heart transplant.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Urology & Nephrology
Greg Knoll, Patricia Campbell, Michael Chasse, Dean Fergusson, Tim Ramsay, Priscilla Karnabi, Jeffrey Perl, Andrew A. House, Joseph Kim, Olwyn Johnston, Rahul Mainra, Isabelle Houde, Dana Baran, Darin J. Treleaven, Lynne Senecal, Lee Anne Tibbles, Marie-Josee Hebert, Christine White, Martin Karpinski, John S. Gill
Summary: This study investigated the use of immunosuppressants in patients with kidney transplant failure and found that prolonged use of immunosuppressants for more than 2 years was not associated with an increased risk of death or hospitalized infection. However, continued use of immunosuppressants did not prevent rejection of the failed allograft or an increase in anti-HLA antibodies.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Immunology
Qiang Fu, Divyansh Agarwal, Kevin Deng, Rudy Matheson, Hongji Yang, Liang Wei, Qing Ran, Shaoping Deng, James F. Markmann
Summary: Efforts to identify biomarkers of tolerance after kidney transplantation have been hindered by small sample sizes and the complex mechanisms involved. Through systematic machine learning exploration, the Best Subset Selection regression approach was found to be the most powerful for predicting kidney graft tolerance, identifying a five-gene feature set and highlighting EBF1 downregulation as a predictive factor for graft rejection and loss.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Hoa Le Mai, Nicolas Degauque, Sabine Le Bot, Marie Rimbert, Karine Renaudin, Richard Danger, Florent Le Borgne, Clarisse Kerleau, Gaelle Tilly, Anais Vivet, Florent Delbos, Alexandre Walencik, Magali Giral, Sophie Brouard
Summary: The study found that the percentage and absolute number of CD28-CD8+ T cells were significantly increased in kidney transplant patients with antibody-mediated rejection (ABMR). Moreover, CD28-CD8+ T cells from patients with ABMR showed a more rigorous response to stimulation compared to their CD28+ counterparts. These findings suggest that differentiated CD28-CD8+ T cells, with increased frequency, number, and function, may play a role in the pathobiology of ABMR.
Article
Immunology
Jung-Woo Seo, Yu Ho Lee, Dong Hyun Tae, Yang Gyun Kim, Ju-Young Moon, Su Woong Jung, Jin Sug Kim, Hyeon Seok Hwang, Kyung-Hwan Jeong, Hye Yun Jeong, So-Young Lee, Byung Ha Chung, Chan-Duck Kim, Jae Berm Park, Junhee Seok, Yeong Hoon Kim, Sang-Ho Lee
Summary: This study aimed to identify novel biomarkers for the diagnosis of acute rejection (AR) in kidney transplant recipients by examining urinary exosomal microRNAs. Candidate microRNAs were selected through urinary exosomal microRNA profiling, meta-analysis, and literature review. A three-microRNA AR signature, consisting of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, showed promising diagnostic power in discriminating recipients with AR from those with stable graft function.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Peter J. Kennel, Alexandre Yahi, Yoshifumi Naka, Donna M. Mancini, Charles C. Marboe, Klaas Max, Kemal Akat, Thomas Tuschl, Elena-Rodica M. Vasilescu, Emmanuel Zorn, Nicholas P. Tatonetti, Paul Christian Schulze
Summary: This study utilized next-generation small RNA sequencing to analyze circulating miRNAs as potential biomarkers for detecting and predicting allograft rejection after heart transplantation. It found three specific miRNAs with significantly increased levels in patients with cardiac rejection and identified potential predictors for acute cellular rejection (ACR) and antibody-mediated rejection (AMR), with hsa-miR-486-5p being strongly associated with acute rejection episodes. Monitoring allograft rejection using circulating miRNAs may offer an alternative to invasive endomyocardial biopsy.
Article
Urology & Nephrology
Christina Lai, Steven J. Chadban, Yik Wen Loh, Tony King-Tak Kwan, Chuanmin Wang, Julian Singer, Paula Niewold, Zheng Ling, Alanna Spiteri, Daniel Getts, Nicholas Jonathan Cole King, Huiling Wu
Summary: Inflammatory monocytes are a major component of acute kidney transplant rejection. This study investigates the therapeutic potential of immune-modifying nanoparticles (IMPs) in preventing kidney allograft rejection. The results show that IMPs significantly reduce acute rejection, improve kidney function, and inhibit inflammatory cell density and cytokine expression. However, IMPs do not offer protection against chronic rejection.
KIDNEY INTERNATIONAL
(2022)
Article
Nanoscience & Nanotechnology
Jinwen Lin, Junhao Lv, Xianping Yu, Xing Xue, Shiping Yu, Huiping Wang, Jianghua Chen
Summary: A genetic engineered membrane-coated nanoparticle called DSA trapper, inspired by the affinity of bacterial proteins for antibodies, is able to efficiently adsorb and clear alloreactive antibodies, restoring single-cell transcriptional heterogeneity. DSA trappers absorbed antibodies through heterophagic clearance, reducing IgG deposition and complement activation, providing an immune tolerant niche for restoration of single-cell genetic architecture. In allogeneic transplantation mice, DSA trapper improved glomerular filtration rate and prolonged survival. Overall, DSA trapper offers a promising approach for treating alloantibody-mediated immune injury.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Urology & Nephrology
Anil Dangi, Irma Husain, Collin Z. Jordan, Shuangjin Yu, Naveen Natesh, Xiling Shen, Jean Kwun, Xunrong Luo
Summary: This study found that resident macrophages in the donor kidney rapidly expanded during the early stages of kidney transplantation and were induced to express high levels of Ccl8. This led to the infiltration of recipient monocytes, their differentiation into resident macrophages, and subsequent expression of Ccl8. Enhanced infiltration of recipient T cells followed. Targeting the CCL8-CCR8 axis shows promise for reducing early kidney allograft inflammation.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Urology & Nephrology
Rania El Fekih, James Hurley, Vasisht Tadigotla, Areej Alghamdi, Anand Srivastava, Christine Coticchia, John Choi, Hazim Allos, Karim Yatim, Juliano Alhaddad, Siawosh Eskandari, Philip Chu, Albana B. Mihali, Isadora T. Lape, Mauricio P. Lima Filho, Bruno T. Aoyama, Anil Chandraker, Kassem Safa, James F. Markmann, Leonardo V. Riella, Richard N. Formica, Johan Skog, Jamil R. Azzi
Summary: The study demonstrates that urinary exosomal mRNA signatures are a powerful and noninvasive tool for screening kidney allograft rejection, with high predictive performance. The signatures can differentiate between different types of rejection and assist clinicians in therapeutic decision making.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Hematology
Marianne Delville, Florence Bellier, Juliette Leon, Roman Klifa, Sabrina Lizot, Helene Vincon, Steicy Sobrino, Romane Thouenon, Armance Marchal, Alexandrine Garrigue, Juliette Olivre, Soeli Charbonnier, Chantal Lagresle-Peyrou, Mario Amendola, Axel Schambach, David Gross, Baptiste Lamarthee, Christophe Benoist, Julien Zuber, Isabelle Andre, Marina Cavazzana, Emmanuelle Six
Summary: The IPEX syndrome is caused by mutations in the FOXP3 gene, leading to loss of Treg function and early development of autoimmune symptoms. Gene transfer of FOXP3 has shown promise in treating IPEX. Using an in vivo model with scurfy mice, researchers demonstrated the potential to rescue the disease after its onset, suggesting that FOXP3 expression can convert CD4(+) T cells into functional Tregs capable of controlling severe autoimmune disease.
Article
Surgery
Yosu Luque, Matthieu Jamme, Olivier Aubert, Arthur Roux, Frank Martinez, Lucile Amrouche, Claire Tinel, Louise Galmiche, Jean-Paul Duong Van Huyen, Francois Audenet, Christophe Legendre, Dany Anglicheau, Marion Rabant
Summary: The utility of zero-time kidney biopsies in accepting expanded criteria donor kidneys is debated, with adverse histology not necessarily correlating with poorer outcomes in terms of graft survival and kidney function among ECD recipients.
TRANSPLANT INTERNATIONAL
(2021)
Article
Urology & Nephrology
Baptiste Lamarthee, Carole Burger, Charlotte Leclaire, Emilie Lebraud, Aniela Zablocki, Lise Morin, Xavier Lebreton, Beatrice Charreau, Renaud Snanoudj, Soeli Charbonnier, Tifanie Blein, Melanie Hardy, Julien Zuber, Simon Satchell, Morgan Gallazzini, Fabiola Terzi, Christophe Legendre, Jean Luc Taupin, Marion Rabant, Claire Tinel, Dany Anglicheau
Summary: The study demonstrates that using human glomerular endothelial cells with all HLA antigens deleted as targets and recapitulating a large array of potential non-HLA antibodies in a single test can confirm the detrimental impact of non-HLA antibodies on microvascular inflammation and graft outcome after kidney transplantation, independent of HLA antibodies.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Review
Urology & Nephrology
Jasper Callemeyn, Baptiste Lamarthee, Alice Koenig, Priyanka Koshy, Olivier Thaunat, Maarten Naesens
Summary: The detection of mismatched human leukocyte antigens by adaptive immune cells is the main cause of transplant rejection. However, recent observations have questioned the traditional dichotomy between T-cell mediated rejection and antibody-mediated rejection, leading to a need for a more integrated view of kidney transplant rejection. This review highlights the gaps in the current classification of rejection, provides an overview of the expanding insights into the mechanisms of allorecognition, and discusses how these insights could improve our understanding and clinical approach to kidney transplant rejection.
KIDNEY INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Baptiste Lamarthee, Armance Marchal, Soeli Charbonnier, Tifanie Blein, Juliette Leon, Emmanuel Martin, Lucas Rabaux, Katrin Vogt, Matthias Titeux, Marianne Delville, Helene Vincon, Emmanuelle Six, Nicolas Pallet, David Michonneau, Dany Anglicheau, Christophe Legendre, Jean-Luc Taupin, Ivan Nemazanyy, Birgit Sawitzki, Sylvain Latour, Marina Cavazzana, Isabelle Andre, Julien Zuber
Summary: The study demonstrates that 4-1BB CAR-Tregs show more dramatic effects in activation and proliferation than CD28 CAR-Tregs, but exhibit reduced in vivo suppressive capacities. Transient exposure to a Treg stabilizing cocktail can sharply improve the in vivo function and expansion of 4-1BB CAR-Tregs. These findings suggest that transient mTOR inhibition can mitigate the negative effects of 4-1BB tonic signaling in Tregs.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Claire Tinel, Baptiste Lamarthee, Jasper Callemeyn, Elisabet Van Loon, Virginia Sauvaget, Lise Morin, Laila Aouni, Marion Rabant, Wilfried Gwinner, Pierre Marquet, Maarten Naesens, Dany Anglicheau
Summary: miRNAs play key roles in antibody-mediated rejection in solid-organ transplantation by regulating cellular functions, such as endothelial cells, epithelial cells, and immune cells, impacting the development of microvascular inflammation as well as renal immune response and electrolyte homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Elisabet Van Loon, Baptiste Lamarthee, Thomas Barba, Sandra Claes, Maarten Coemans, Henriette de Loor, Marie-Paule Emonds, Priyanka Koshy, Dirk Kuypers, Paul Proost, Aleksandar Senev, Ben Sprangers, Claire Tinel, Olivier Thaunat, Amaryllis H. Van Craenenbroeck, Dominique Schols, Maarten Naesens
Summary: Through multiplex assay, we found that kidney transplant patients with donor-specific anti-human leukocyte antigen antibodies and histological rejection have increased levels of pro-inflammatory cytokines in blood. Even in patients without histological rejection, elevated pro-inflammatory cytokine levels can be observed. These findings challenge the concept of histology as the gold standard for identifying ongoing allo-immune activation after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Elisabet Van Loon, Baptiste Lamarthee, Henriette de Loor, Amaryllis H. Van Craenenbroeck, Sophie Brouard, Richard Danger, Magali Giral, Jasper Callemeyn, Claire Tinel, Alvaro Cortes Calabuig, Priyanka Koshy, Ben Sprangers, Dirk Kuypers, Wilfried Gwinner, Dany Anglicheau, Pierre Marquet, Maarten Naesens
Summary: Molecular changes in kidney transplant injury, especially immune cell activation pathways, were studied in peripheral blood and kidney allograft samples, highlighting the importance of immune activation in kidney transplant pathology despite strong immunosuppressant treatment.
KIDNEY INTERNATIONAL
(2022)
Review
Immunology
Emilie Lebraud, Maeva Eloudzeri, Marion Rabant, Baptiste Lamarthee, Dany Anglicheau
Summary: Antibody-mediated rejection is a significant cause of graft failure after kidney transplantation. This review discusses the different pathogenic processes underlying this rejection and highlights the role of non-HLA antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Claire Gerard, Marine Thebault, Baptiste Lamarthee, Coraline Genet, Florine Cattin, Andrea Brazdova, Nona Janikashvili, Claudie Cladiere, Marion Ciudad, Sethi Ouandji, Thibault Ghesquiere, Helene Greigert, Claire Tinel, Olivier Adotevi, Philippe Saas, Maxime Samson, Sylvain Audia, Bernard Bonnotte
Summary: Recently developed cell-based therapies have shown potential for mitigating graft-versus-host disease (GvHD). CD14+HuMoSC supernatant can reduce GvHD symptoms by inhibiting T cell proliferation and CD8 cell activity, and it can also maintain its immunosuppressive properties in an inflammatory environment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Aleksandar Senev, Elisabet Van Loon, Evelyne Lerut, Maarten Coemans, Jasper Callemeyn, Liesbeth Daniels, Johan Kerkhofs, Priyanka Koshy, Dirk Kuypers, Baptiste Lamarthee, Ben Sprangers, Claire Tinel, Amaryllis H. Van Craenenbroeck, Vicky Van Sandt, Marie-Paule Emonds, Maarten Naesens
Summary: There is an association between human leukocyte antigen molecular mismatches and T-cell-mediated rejection (TCMR). The occurrence of TCMR is mainly affected by the PIRCHE-II scores of HLA-DRB1 and HLA-DQB1.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Immunology
Claire Tinel, Baptiste Lamarthee, Stephane Gazut, Elisabet Van Loon, Florent Von Tokarski, Aurelien Benon, Virginia Sauvaget, Victor Garcia-Paredes, Mickael Menager, Lise Morin, Laila Aouni, Nicolas Cagnard, Marion Rabant, Christophe Legendre, Fabiola Terzi, Marie Essig, Wilfried Gwinner, Maarten Naesens, Pierre Marquet, Dany Anglicheau
Summary: Increasing evidence suggests that microRNAs are involved in the pathophysiology of renal diseases, including kidney transplantation. In this study, the researchers investigated the changes in circulating microRNA expression and their involvement in antibody-mediated rejection. They found that certain microRNAs were significantly decreased in samples with rejection, and these microRNAs were associated with myeloid-related pathways and CD14+ monocytes.
Article
Multidisciplinary Sciences
Baptiste Lamarthee, Jasper Callemeyn, Yannick Van Herck, Asier Antoranz, Dany Anglicheau, Patrick Boada, Jan Ulrich Becker, Tim Debyser, Frederik De Smet, Katrien De Vusser, Maeva Eloudzeri, Amelie Franken, Wilfried Gwinner, Priyanka Koshy, Dirk Kuypers, Diether Lambrechts, Pierre Marquet, Virginie Mathias, Marion Rabant, Minnie M. Sarwal, Aleksandar Senev, Tara K. Sigdel, Ben Sprangers, Olivier Thaunat, Claire Tinel, Thomas Van Brussel, Amaryllis Van Craenenbroeck, Elisabet Van Loon, Thibaut Vaulet, Francesca Bosisio, Maarten Naesens
Summary: Although kidney allograft failure is classified as either T cell- or antibody-mediated, this distinction is not always clear in all patients, emphasizing the need for better characterization of allograft tissue. The authors used single-cell RNA sequencing and multiplex imaging to analyze the transcriptomes and spatial profiles of allograft tissue from patients with different degrees of rejection severity. The study identified specific cell types and gene expression signatures associated with rejection, highlighting the involvement of innate immune cells in allograft rejection and suggesting potential therapeutic targets to improve graft longevity.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Surgery
E. Van Loon, T. Barba, B. Lamarthee, A. Senev, O. Thaunat, D. Schols, M. Naesens
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)