Editorial Material
Biochemistry & Molecular Biology
Nissrin Alachkar, Nada Alachkar
Summary: Diagnosing kidney allograft rejection is complex and subjective, but an automated Banff classification could make assessment easier and improve accuracy.
Article
Biochemistry & Molecular Biology
Bertrand Chauveau, Anne-Aurelie Raymond, Sylvaine Di Tommaso, Jonathan Visentin, Agathe Vermorel, Nathalie Dugot-Senant, Cyril Dourthe, Jean-William Dupuy, Julie Dechanet-Merville, Jean-Paul Duong Van Huyen, Marion Rabant, Lionel Couzi, Frederic Saltel, Pierre Merville
Summary: This study used proteomics to investigate the glomerular proteome modification in antibody-mediated rejection (ABMR) in kidney transplantation. It identified several proteins related to cellular stress, leukocyte activation, and tissue remodeling that were deregulated in ABMR. These findings may have implications for the diagnosis and treatment of ABMR.
Article
Medicine, General & Internal
Marius Andreas Koslik, Justa Friebus-Kardash, Falko Markus Heinemann, Andreas Kribben, Jan Hinrich Braesen, Ute Eisenberger
Summary: This study analyzed the effect of different treatment approaches for ABMR on renal allograft survival and compared the treatment effects with or without DSAs. Results showed that long-term application of IVIG was more favorable for DSA-positive recipients, while intensification of maintenance immunosuppression was more effective for recipients without DSAs.
FRONTIERS IN MEDICINE
(2022)
Article
Medicine, General & Internal
Capucine Arrive, Marvin Jacquet, Elodie Gautier-Veyret, Thomas Jouve, Johan Noble, Dorothee Lombardo, Lionel Rostaing, Francoise Stanke-Labesque
Summary: The study suggests that early exposure to tocilizumab may be associated with macroalbuminuria within the first six months in patients with chronic antibody-mediated rejection (CAMR) of kidney transplant.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Urology & Nephrology
Brian J. Nankivell, Chow H. P'Ng, Meena Shingde
Summary: C4d(glom) is a promising diagnostic biomarker of endothelial interaction with antibody, which improves the immunologic classification of transplant glomerulopathy and enhances the accuracy of diagnosing late antibody-mediated rejection.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Pharmacology & Pharmacy
Zhou Hang, Jintao Wei, Ming Zheng, Zeping Gui, Hao Chen, Li Sun, Shuang Fei, Zhijian Han, Jun Tao, Zijie Wang, Ruoyun Tan, Min Gu
Summary: This study found that IGT can inhibit the polarization of M1 macrophages, alleviate the pathological changes in ABMR, reduce DSA titers, and mitigate the pathogenesis of ABMR by targeting KLF4.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Surgery
Olga A. Timofeeva, Jason Choe, Mohamed Alsammak, Edward J. Yoon, Steven S. Geier, Leena Mathew, Amanda McCollick, Kevin Carney, Jenny Au, Adam Diamond, Jonathan A. Galli, Kartik Shenoy, Albert Mamary, Sameep Sehgal, Patrick Mulhall, Yoshiya Toyoda, Norihisa Shigemura, Francis Cordova, Gerald Criner, James C. Brown
Summary: This study investigated how DSA characteristics can predict response to therapeutic plasma exchange and inform patient prognosis after treatment. Through categorizing patients into responders, partial responders, and nonresponders, the study highlighted the importance of MFI values in predicting patient response and survival, suggesting strategies for potentially more aggressive treatment for patients who may not respond to standard protocols.
TRANSPLANT INTERNATIONAL
(2021)
Review
Urology & Nephrology
Hajime Sasaki, Tatsu Tanabe, Takahiro Tsuji, Kiyohiko Hotta
Summary: Chronic antibody-mediated rejection is a significant cause of late-stage kidney graft loss, primarily driven by donor-specific antibodies. These antibodies activate complement, leading to tissue injury and coagulation. Complement activation further promotes inflammation and endothelial injury. This review discusses the development of de novo donor-specific antibodies, the mechanisms underlying chronic antibody-mediated rejection, current treatment options, and the latest biomarkers for early detection.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Immunology
Konstantin Doberer, Johannes Klaeger, Guido A. Gualdoni, Katharina A. Mayer, Farsad Eskandary, Evan A. Farkash, Hermine Agis, Thomas Reiter, Roman Reindl-Schwaighofer, Markus Wahrmann, Gerald Cohen, Helmuth Haslacher, Gregor Bond, Ingrid Simonitsch-Klupp, Philip F. Halloran, Georg A. Boehmig
Summary: The study highlights the potential of targeting CD38 for plasma cell and NK cell depletion in treating AMR. The use of daratumumab in a kidney allograft recipient with chronic active AMR led to significant improvements in immune cell counts, donor-specific antibody levels, and rejection-related gene expression patterns. This innovative treatment concept shows promise for future trials in organ transplantation research.
Review
Pharmacology & Pharmacy
Lukas K. van Vugt, Maaike R. Schagen, Annelies de Weerd, Marlies Ej Reinders, Brenda Cm de Winter, Dennis A. Hesselink
Summary: Kidney transplant rejection remains a clinical problem, and current therapy is unsatisfactory. This review discusses novel and investigational drugs for the treatment of kidney transplant rejection, as well as potential therapeutic strategies and future directions.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Immunology
Zhe Yang, Fei Han, Tao Liao, Haofeng Zheng, Zihuan Luo, Maolin Ma, Jiannan He, Lei Li, Yongrong Ye, Rui Zhang, Zhengyu Huang, Yannan Zhang, Qiquan Sun
Summary: Artemisinin demonstrates significant immunosuppressive effects in rat cardiac transplantation model, attenuating rejection reactions and prolonging allograft survival. By targeting multiple effector cells, artemisinin effectively reduces T cell-mediated rejection and antibody-mediated rejection, showing potential for clinical use in transplant rejection prevention.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Health Care Sciences & Services
Hongmei Jiang, Hui Guo, Bo Yang, Yuanyuan Zhao, Lai Wei, Zhishui Chen, Dong Chen
Summary: This case series explores the characteristics and outcomes of acute AMR in liver transplant recipients with autoimmune liver disease (ALD). The incidence of acute AMR in ALD patients was higher compared to non-ALD recipients. Individualized therapies based on clinical manifestations resulted in good prognoses for most patients.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Immunology
Tara K. Sigdel, Paul A. Fields, Juliane Liberto, Izabella Damm, Maggie Kerwin, Jill Hood, Parhom Towfighi, Marina Sirota, Harlan S. Robins, Minnie M. Sarwal
Summary: In this study, researchers analyzed the T-cell repertoire in kidney transplant recipients and found that changes in the repertoire are associated with post-transplant rejection episodes. T-cell receptor sequencing may serve as a valuable tool for predicting rejection risk after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Katarzyna Nowanska, Miroslaw Banasik, Piotr Donizy, Katarzyna Koscielska-Kasprzak, Slawomir Zmonarski, Krzysztof Letachowicz, Dorota Kaminska, Oktawia Mazanowska, Hanna Augustyniak-Bartosik, Andrzej Tukiendorf, Anna Chudiak, Tomasz Dawiskiba, Agnieszka Halon, Magdalena Krajewska
Summary: The study evaluated the expression of ETA receptors in glomeruli of renal transplant patients, finding positive staining in 8.7% of patients. Patients with positive ETA receptor expression in glomeruli were more likely to develop antibody-mediated rejection (AMR), with a higher graft loss rate in the first year after biopsy compared to patients without ETA receptor expression in glomeruli.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Hannes Vietzen, Peter Jaksch, Elisabeth Puchhammer-Stoeckl
Summary: In lung transplant recipients, specific UL40 peptide variants of HCMV strains are associated with the development of ABMR, leading to a shift towards a highly cytotoxic CD16+NKG2C+ NK cell population.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(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)
Review
Immunology
Imran J. Anwar, Isabel F. DeLaura, Qimeng Gao, Joseph Ladowski, Annette M. Jackson, Jean Kwun, Stuart J. Knechtle
Summary: Despite the significant improvement in kidney transplantation outcomes over the last decades, long-term results remain unsatisfactory due to antibody-mediated rejection. Currently, there are no FDA-approved regimens for this treatment, but several clinical trials are underway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Surgery
Imran J. J. Anwar, Brian Ezekian, Isabel DeLaura, Miriam Manook, Paul Schroder, Janghoon Yoon, Verna Curfman, Evelyn Branum, Julia Messina, Melissa Harnois, Sallie R. R. Permar, Alton B. B. Farris, Jean Kwun, Stuart J. J. Knechtle
Summary: This study evaluates the desensitization of highly sensitized kidney transplant patients by targeting plasma cells and interleukin-6 receptors. The combination therapy of carfilzomib and tocilizumab shows promising results in reducing donor-specific antibodies and preventing the expansion of B cells, leading to better survival rates compared to carfilzomib monotherapy.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Immunology
Imran J. Anwar, Isabel DeLaura, Joseph Ladowski, Qimeng Gao, Stuart J. Knechtle, Jean Kwun
Summary: Aberrant activation of the complement system contributes to solid-organ graft dysfunction and failure, particularly in kidney transplantation. Various mechanisms of rejection in kidney transplantation involve the complement system, which has led to the exploration of complement inhibitors as potential therapeutic options. However, the complexity of the system makes it challenging to fully understand and target for treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Riley E. Scalzo, Scott L. Sanoff, Aparna S. Rege, Jean Kwun, Stuart J. Knechtle, Laura Barisoni, Jennifer S. Byrns
Summary: There is a growing interest in the use of daratumumab for desensitization and potential treatment for antibody-mediated rejection in solid organ transplant. However, ongoing investigations have shown potential immunologic concerns with daratumumab, particularly an increase in populations of CD4-positive cytotoxic T cells and CD8-positive helper T cells that could result in acute T cell-mediated rejection. This case report presents the first documented case of early severe T-cell mediated rejection in a low-immunologic-risk living-donor kidney transplant recipient who received daratumumab for multiple myeloma maintenance prior to transplant.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Article
Biochemical Research Methods
Isabel DeLaura, Paul M. Schroder, Janghoon Yoon, Joseph Ladowski, Imran J. Anwar, Brian Ezekian, Robin Schmitz, Zachary W. Fitch, Jean Kwun, Stuart J. Knechtle
Summary: This study describes the first in vitro nonhuman primate model of B cell activation and proliferation using both naive and allosensitized samples. This model provides an opportunity for exploring B cell mechanisms and developing novel therapeutics, and is a preliminary step in the development of an in vitro germinal center model.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Article
Multidisciplinary Sciences
Miriam Manook, Danae Olaso, Imran J. Anwar, Janghoon Yoon, Isabel Delaura, Yeeun Bae, Dimitrios Moris, Brian Shaw, Mingqing Song, Alton B. Farris, Annette Jackson, Jean Kwun, Stuart Knechtle
Summary: This study examined the effectiveness of costimulation blockade and proteasome inhibition for desensitization in female NHPs sensitized by pregnancy alone. The results showed that the addition of belatacept and tacrolimus significantly prolonged graft survival and suppressed the production of donor-specific antibodies.
Article
Multidisciplinary Sciences
Ranjith P. Anand, Jacob V. Layer, David Heja, Takayuki Hirose, Grace Lassiter, Daniel J. Firl, Violette B. Paragas, Adam Akkad, Sagar Chhangawala, Robert B. Colvin, Russell J. Ernst, Nicholas Esch, Kristen Getchell, Alexandra K. Griffin, Xiaoyun Guo, Katherine C. Hall, Paula Hamilton, Lokesh A. Kalekar, Yinan Kan, Ahmad Karadagi, Feng Li, Susan C. Low, Rudy Matheson, Claudia Nehring, Ryo Otsuka, Matthew Pandelakis, Robert A. Policastro, Rebecca Pols, Luis Queiroz, Ivy A. Rosales, William T. Serkin, Kathryn Stiede, Toshihide Tomosugi, Yongqiang Xue, Gabriel E. Zentner, David Angeles-Albores, J. Chris Chao, Juliet N. Crabtree, Sierra Harken, Nicole Hinkle, Tania Lemos, Mailin Li, Lorena Pantano, Denise Stevens, Omar D. Subedar, Xiaoqing Tan, Shiyi Yin, Imran J. Anwar, David Aufhauser, Saverio Capuano, Dixon B. Kaufman, Stuart J. Knechtle, Jean Kwun, Dhanansayan Shanmuganayagam, James F. Markmann, George M. Church, Mike Curtis, Tatsuo Kawai, Michele E. Youd, Wenning Qin
Summary: This study explores the design, creation, and long-term function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The study shows successful preclinical studies of renal xenotransplantation in nonhuman primates and brings us closer to clinical trials of genetically engineered porcine renal grafts.
Meeting Abstract
Immunology
Joe Ladowski, Henry Chapman, Imran J. Anwar, Isabel DeLaura, Annette Jackson, Stuart J. Knechtle, Bruce Rogers, Jean Kwun
Article
Medicine, Research & Experimental
Isabel DeLaura, Joanna Zikos, Imran J. Anwar, Janghoon Yoon, Joseph Ladowski, Annette Jackson, Koen Van Rompay, Diogo Magnani, Stuart J. Knechtle, Jean Kwun
Summary: Highly sensitized patients face barriers to kidney transplantation, IdeS has been trialed as desensitization prior to kidney transplant, effectively cleaving donor-specific antibody, but with rebound. In nonhuman primates, IdeS successfully reduced various IgG populations, showing potential for clinical xenotransplantation, but may need optimization with other agents for prolonged efficacy.
XENOTRANSPLANTATION
(2023)
Article
Urology & Nephrology
Robin Schmitz, Zachary W. Fitch, Miriam Manook, Paul M. Schroder, Ashley Y. Choi, Danae Olaso, Janghoon Yoon, Yeeun Bae, Brian Shaw, Mingqing Song, Maragatha Kuchibhatla, Alton B. Farris, Allan Kirk, Jean Kwun, Stuart J. Knechtle
Summary: This study investigated kidney transplants in highly sensitized nonhuman primates, showing that belatacept-based immunosuppression significantly reduced the risk of antibody-mediated rejection and controlled post-transplant humoral responses. The study suggests further investigation of belatacept-based immunosuppression in human clinical trials to improve graft survival in sensitized recipients.
Meeting Abstract
Surgery
I. DeLaura, I. Anwar, M. Manook, D. Olaso, J. Yoon, R. Baldi, A. Jackson, S. Knechtle, J. Kwun
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Surgery
I. DeLaura, M. Manook, D. Olaso, J. Yoon, R. Baldi, S. Knechtle, J. Kwun
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Surgery
M. Manook, D. Olaso, I. Anwar, J. Yoon, M. Song, A. B. Farris, K. Stiede, K. Hall, M. Youd, S. Knechtle, J. Kwun
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Surgery
M. Manook, I. Anwar, R. Schmitz, Z. Fitch, J. Yoon, A. Jackson, J. Kwun, S. Knechtle
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)