Article
Surgery
Vincent Pernin, Nicole Bec, Anais Beyze, Alexis Bourgeois, Ilan Szwarc, Coralie Champion, Anthony Chauvin, Celine Rene, Georges Mourad, Pierre Merville, Jonathan Visentin, Helene Perrochia, Lionel Couzi, Christian Larroque, Moglie Le Quintrec
Summary: The glycosylation profile of IgG3 dnDSA is associated with the risk of ABMR occurrence, with low sialylation and high GlcNAc bisection being potentially predictive factors. Further studies are needed to confirm the clinical significance of DSA glycosylation in predicting ABMR and graft survival.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Surgery
Edmund Huang, Angela Q. Maldonado, Christian Kjellman, Stanley C. Jordan
Summary: Imlifidase, derived from Streptococcus pyogenes, is a novel agent with potential for HLA desensitization and antibody-mediated rejection in kidney transplantation. Clinical trials have shown rapid degradation of anti-HLA donor-specific antibodies, facilitating HLA-incompatible transplantation. Early experiences with imilfidase highlight considerations regarding kinetics of antibodies, timing of complementary therapies, and interference with cross match assays.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Daniel S. Ramon, Danielle M. Troop, Theresa N. Kinard, Caroline C. Jadlowiec, Margaret S. Ryan, Winston R. Hewitt, Linda G. Olsen, Andres Jaramillo, Timucin Taner, Raymond L. Heilman
Summary: Simultaneous liver-kidney transplant (SLKT) with donor-specific antibodies (DSA) is common, but after a second liver transplant, an abrupt increase in DSA levels against the kidney led to antibody-mediated rejection (AMR). The clearance of antibodies depended on the HLA antigens expressed by the transplanted liver cells.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Jasper Callemeyn, Heleen Ameye, Evelyne Lerut, Aleksandar Senev, Maarten Coemans, Elisabet Van Loon, Ben Sprangers, Vicky Van Sandt, Maud Rabeyrin, Valerie Dubois, Olivier Thaunat, Dirk Kuypers, Marie-Paule Emonds, Maarten Naesens
Summary: The study evaluated the changes in the Banff classification for antibody-mediated rejection (ABMR) and their impact on transplant outcomes and case numbers, finding an increase in cases from Banff'01 to Banff'13 and variable outcomes for reclassified sABMR in Banff'17. The clinical and histological heterogeneity of ABMR is inadequately represented in a binary classification system.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Jason M. Zimmerer, Jing L. Han, Chelsea M. Peterson, Qiang Zeng, Bryce A. Ringwald, Clarissa Cassol, Sachi Chaudhari, Madison Hart, Jessica Hemminger, Anjali Satoskar, Mahmoud Abdel-Rasoul, Jiao-Jing Wang, Robert T. Warren, Zheng J. Zhang, Christopher K. Breuer, Ginny L. Bumgardner
Summary: CCR5 KO kidney transplant recipients have high levels of alloantibodies and develop pathology similar to human antibody-mediated rejection. The deficiency in quantity and function of alloprimed CXCR5(+)CD8(+) T cells contributes to high alloantibody and AMR in CCR5 KO recipient mice, which can be rescued with adoptive cell therapy using alloprimed CXCR5(+)CD8(+) T cells.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Philip F. Halloran, Katelynn S. Madill-Thomsen, Shane Pon, Majid L. N. Sikosana, Georg A. Boehmig, Jonathan Bromberg, Gunilla Einecke, Farsad Eskandary, Gaurav Gupta, Luis G. Hidalgo, Marek Myslak, Ondrej Viklicky, Agnieszka Perkowska-Ptasinska
Summary: In 398 kidney transplant biopsies with molecular antibody-mediated rejection, the 150 DSA-negative cases are earlier, less intense, and mostly C4d-negative, but use identical molecular mechanisms and have the same risk of graft loss as the 248 DSA-positive cases.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Philip F. Halloran, Georg A. Bohmig, Jonathan S. Bromberg, Klemens Budde, Gaurav Gupta, Gunilla Einecke, Farsad Eskandary, Katelynn Madill-Thomsen, Jeff Reeve
Summary: The study found that certain injury elements in kidney transplant are selective for specific pathologic mechanisms, with Dimension 3 being a newly discovered dimension involving genes related to epithelial polarity.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Maeva Massat, Nicolas Congy-Jolivet, Anne-Laure Hebral, Laure Esposito, Olivier Marion, Audrey Delas, Magali Colombat, Stanislas Faguer, Nassim Kamar, Arnaud Del Bello
Summary: This study found that monthly infusions of tocilizumab did not alter the progression of antibodies in patients with antibody-mediated rejection resistant to standard of care therapy. There were no significant differences in graft survival and decline in renal function between patients who received tocilizumab and those who did not. Despite a decrease in inflammation and tubulitis scores, the course of antibody-mediated lesions and chronic glomerulopathy were similar in both groups.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
D. Marshall Brinkley, MariaSanta Mangione, Sallyanne C. C. Fossey, Kimberly M. Harrison, Sandip Zalawadiya, Aniket S. S. Rali, Hasan K. K. Siddiqi, JoAnn Lindenfeld, Kelly H. H. Schlendorf
Summary: We studied the efficacy of a desensitization regimen in heart transplant candidates and found that it effectively removed C1q negative antibodies and decreased HLA class I antibodies. This led to successful transplants in 76% of patients with a 1-year survival rate of 89%. The desensitization protocol was modestly effective for class I antibodies and combined with selective crossing of C1q negative antigens.
CLINICAL TRANSPLANTATION
(2023)
Article
Surgery
Marc Labriffe, Jean-Baptiste Woillard, Wilfried Gwinner, Jan-Hinrich Braesen, Dany Anglicheau, Marion Rabant, Priyanka Koshy, Maarten Naesens, Pierre Marquet
Summary: In this study, artificial intelligence classifiers were used to interpret kidney graft biopsies and diagnose rejection. The classifiers showed high sensitivity and specificity, and had excellent concordance with the Banff classification rules and expert diagnoses. This research demonstrates the potential of using AI classifiers in improving the interpretation of kidney graft biopsies.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Gunilla Einecke, Jeff Reeve, Gaurav Gupta, Georg A. Boehmig, Farsad Eskandary, Jonathan S. Bromberg, Klemens Budde, Philip F. Halloran
Summary: In this study, the focus was on clinical and molecular features of kidney transplant patients after indication biopsy to predict the risk of transplant failure. The results showed that factors such as estimated GFR, proteinuria, time posttransplant, donor-specific antibody, as well as molecular and histologic features reflecting injury were more important predictors of failure compared to rejection activity.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Urology & Nephrology
Elodie Bailly, Camila Macedo, Jason Ossart, Kevin Louis, Xinyan Gu, Bala Ramaswami, Carol Bentlejewski, Adriana Zeevi, Parmjeet Randhawa, Carmen Lefaucheur, Diana Metes
Summary: CD160+ IL-21R+ NK cells play a crucial role in kidney allograft antibody-mediated rejection. These cells exhibit distinct phenotypic and functional characteristics and are involved in the rejection response by activating multiple signaling pathways.
KIDNEY INTERNATIONAL
(2023)
Review
Immunology
Lara Cabezas, Thomas Jouve, Paolo Malvezzi, Benedicte Janbon, Diane Giovannini, Lionel Rostaing, Johan Noble
Summary: Chronic kidney disease is a significant public-health problem, and kidney transplantation is a better alternative to dialysis. Antibody-mediated rejection is a major complication following kidney transplantation. TCZ appears to be a safe and effective treatment for managing antibody-mediated rejection and reducing injury.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Michiel G. H. Betjes, Dave L. Roelen, Madelon van Agteren, Judith Kal-van Gestel
Summary: This study documents the causes of graft loss many years after kidney transplantation. Rejection is the main cause, with antibody-mediated rejection becoming more common over time. Death is also an important risk factor for graft failure. Recipient age, time after transplantation, and the presence of donor-specific antibodies before transplantation determine the contribution and type of rejection involved in graft loss.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Nicola Bertazza Partigiani, Susanna Negrisolo, Andrea Carraro, Diana Marzenta, Elisabetta Manaresi, Giorgio Gallinella, Luisa Barzon, Elisa Benetti
Summary: Viral infections can lead to transplant dysfunction and may play a role in rejection. Analysis of protocol biopsies in 106 children at different time points after transplantation showed an increased prevalence of intrarenal viral infection between 6 and 12 months. Specifically, Parvovirus B19 infection was associated with antibody-mediated rejection. Monitoring and treatment of Parvovirus B19 infection in the early post-transplant period is important.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
William Irish, Peter Nickerson, Brad C. Astor, Edward Chong, Chris Wiebe, Francesc Moreso, Daniel Seron, Marta Crespo, Larry Gache, Arjang Djamali
Summary: This study examined the relationship between eGFR changes and graft failure in patients with active antibody-mediated rejection after kidney transplantation. The findings suggest a significant decline in eGFR within the first 12 months postdiagnosis of active AMR, with potential improvements in eGFR slope associated with decreased death-censored graft failure rates.
Article
Surgery
Fadi Issa, Samuel Strober, Joseph R. Leventhal, Tatsuo Kawai, Dixon B. Kaufman, Josh Levitsky, Megan Sykes, Valeria Mas, Kathryn J. Wood, Nancy Bridges, Lisbeth A. Welniak, Sindhu Chandran, Joren C. Madsen, Peter Nickerson, Anthony J. Demetris, Fadi G. Lakkis, Angus W. Thomson
Summary: The International Workshop on Clinical Transplant Tolerance focuses on the progress of studies involving immunosuppression minimization or withdrawal in solid organ transplantation. The latest workshop showcased clinical trials utilizing donor or recipient cell therapy in combination with organ transplantation to minimize or withdraw immunosuppressive drugs. Additionally, mechanisms of tolerance and potential predictors/biomarkers were discussed, as well as strategies to enhance safety and improve patient selection/risk stratification for clinical trials in hematopoietic cell transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Scott Davis, Christopher Wiebe, Kristen Campbell, Cheri Anobile, Michael Aubrey, Erik Stites, Monica Grafals, Elizabeth Pomfret, Peter Nickerson, James E. Cooper
Summary: This study evaluated HLA-DR and -DQ molecular mismatch to predict the risk of DSAs in renal transplant patients, and found that different levels of tacrolimus exposure may modulate this risk. The results showed that HLA molecular mismatch can serve as a reproducible and clinically relevant tool to stratify patients by alloimmune risk and help guide personalized immunosuppression management.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Review
Urology & Nephrology
Anat R. Tambur, Vasilis Kosmoliaptsis, Frans H. J. Claas, Roslyn B. Mannon, Peter Nickerson, Maarten Naesens
Summary: The importance of HLA matching in kidney allocation algorithms, especially in the US, has decreased due to the introduction of modern immunosuppression, aiming to reduce ethnic/racial disparities in access to transplantation. However, chronic antibody-mediated rejection, primarily caused by de novo antibodies against mismatched donor HLA, remains a leading cause of graft loss, affecting the availability of second transplants for sensitized patients. Recommendations include examining the impact of donor-recipient HLA class II and reconsidering best practices to reduce inequalities while optimizing patient outcomes.
KIDNEY INTERNATIONAL
(2021)
Article
Surgery
Christie Rampersad, Robert Balshaw, Ian W. Gibson, Julie Ho, Jamie Shaw, Martin Karpinski, Aviva Goldberg, Patricia Birk, David N. Rush, Peter W. Nickerson, Chris Wiebe
Summary: The study shows that in kidney transplant recipients receiving tacrolimus/mycophenolate-based maintenance therapy, TCMR is common, correlates with HLA-DR/DQ molecular mismatch scores, and is associated with the risk of graft loss.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Surgery
Julie Ho, George N. Okoli, Rasheda Rabbani, Otto L. T. Lam, Viraj K. Reddy, Nicole Askin, Christie Rampersad, Aaron Trachtenberg, Chris Wiebe, Peter Nickerson, Ahmed M. Abou-Setta
Summary: This study analyzed the effectiveness of T cell-mediated rejection therapy in patients on tacrolimus and mycophenolic acid, showing that 39% of patients continued to have rejection after treatment. Pulse steroids and augmented maintenance immunosuppression were commonly used, but there was considerable practice heterogeneity.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Immunology
Chris Wiebe, Peter W. Nickerson
Summary: This review discusses HLA molecular mismatch as a potential prognostic and predictive biomarker at the time of transplantation, highlighting the retrospective data that supports single molecule risk categorization.
Article
Surgery
Andreas H. Kramer, Kerry Holliday, Sean Keenan, George Isac, Demetrius J. Kutsogiannis, Norman M. Kneteman, Peter Kim, Adrian Robertson, Peter W. Nickerson, Lee Anne Tibbles
Summary: Premortem heparin is widely used in DCD cases, but there is variability in timing and dose. The timing and dose of heparin administration did not affect kidney outcomes, but may have an impact on biliary complications following liver transplantation.
CANADIAN JOURNAL OF SURGERY
(2022)
Article
Medicine, General & Internal
Aimee J. Sarti, Stephanie Sutherland, Maureen Meade, Sam Shemie, Angele Landriault, Brandi Vanderspank-Wright, Sabira Valiani, Sean Keenan, Matthew J. Weiss, Kim Werestiuk, Andreas H. Kramer, Joann Kawchuk, Stephen Beed, Sonny Dhanani, Giuseppe Pagliarello, Michael Chasse, Ken Lotherington, Mary Gatien, Kim Parsons, Jennifer A. Chandler, Peter Nickerson, Pierre Cardinal
Summary: Through in-depth interviews with family members in Canada, we found that families need comprehensive support during the organ donation process. This includes access to individuals with shared experiences, support during specific moments, and better support during critical transitions. Improvements are also needed in establishing connections with recipients and providing support after donation.
CANADIAN MEDICAL ASSOCIATION JOURNAL
(2022)
Editorial Material
Urology & Nephrology
Chris Wiebe, Peter W. Nickerson, Vasilis Kosmoliaptsis
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Urology & Nephrology
Donald E. Hricik, Brian Armstrong, Tarek Alhamad, Daniel C. Brennan, Jonathan S. Bromberg, Suphamai Bunnapradist, Sindhu Chandran, Robert L. Fairchild, David P. Foley, Richard Formica, Ian W. Gibson, Karen Kesler, S. Joseph Kim, Roslyn B. Mannon, Madhav C. Menon, Kenneth A. Newell, Peter Nickerson, Jonah Odim, Emilio D. Poggio, Randall Sung, Ron Shapiro, Kathryn Tinckam, Flavio Vincenti, Peter S. Heeger
Summary: This study tested the effects of blocking TNFa during kidney transplantation. The results showed that there was no significant difference in eGFR at 24 months between the IFX and placebo groups, but the IFX group had higher rates of BK virus infection.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Review
Surgery
Peter W. W. Nickerson
Summary: Chronic active antibody-mediated rejection (caAMR) is a major cause of late graft loss in kidney transplantation, and effective therapies are currently lacking. This review discusses the rationale and early evidence supporting the use of targeting the IL6/IL6R pathway in caAMR kidney transplant recipients, which is the focus of the IMAGINE study.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Anat R. Tambur, Oriol Bestard, Patricia Campbell, Anita S. Chong, Marta Crespo, Mandy L. Ford, Howard M. Gebel, Sebastiaan Heidt, Michelle Hickey, Annette Jackson, Vasilis Kosmoliaptsis, Carmen Lefaucheur, Kevin Louis, Roslyn B. Mannon, Michael Mengel, Anna Morris, David F. Pinelli, Elaine F. Reed, Carrie Schinstock, Jean-Luc Taupin, Nicole Valenzuela, Chris Wiebe, Peter Nickerson
Summary: The Sensitization in Transplantation: Assessment of Risk workgroup, a collaboration between the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics, aims to improve histocompatibility testing in support of solid organ transplantation. This report updates previous discussions and introduces two areas of exploration: non-human leukocyte antigen antibodies and the use of human leukocyte antigen antibody testing to evaluate antibody-removal therapies.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Surgery
Carmen Lefaucheur, Kevin Louis, Anna B. Morris, Jean-Luc Taupin, Peter Nickerson, Anat R. Tambur, Howard M. Gebel, Elaine F. Reed
Summary: This consensus report provides clinical practice recommendations in kidney, heart, lung, and liver transplantation based on expert assessment of quality and strength of evidence regarding the relationship between anti-HLA donor-specific antibodies and transplant outcome. The recommendations address major clinical problems in transplantation, including the clinical implications of positive posttransplant DSA detection, the relevance of posttransplant DSA assessment for diagnosis and treatment management, and the relevance of posttransplant DSA for allograft prognosis and risk stratification.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
Peter W. Nickerson, Georg A. Boehmig, Steve Chadban, Deepali Kumar, Roslyn B. Mannon, Teun van Gelder, James C. Lee, Scott Adler, Edward Chong, Arjang Djamali
Summary: This article describes the design of a Phase 3 clinical trial investigating the safety and efficacy of Clazakizumab in kidney transplant recipients with chronic active AMR. The trial aims to utilize eGFR slope as a surrogate endpoint for graft loss and is the largest placebo-controlled trial in this patient population. The findings of this study will be crucial in addressing the unmet need for novel therapies for chronic active AMR.
