The detailed program, faculty and abstracts are now available online!



Compiled by: Valeria Mas, Jennifer McDaniels
Editor: Enver Akalin

TTS Educational Committee started Hot Off the Press in April 2020, after the COVID-19 pandemic, to review important 3-5 articles related to COVID-19 and transplantation. The aim was to inform TTS members about new and important publications. The initiative has received good feedback. We plan to continue New Hot Off The Press weekly to and feature important manuscripts from high impact journals on the following topics: (view right panel).

  • Basic science + Immunology
  • Kidney transplantation
  • Liver transplantation
  • Heart and lung transplantation
  • Infectious disease
  • Tissue typing and transplant pathology
  • Others, including organ allocation, organ preservation, ethical issues, pediatric transplantation

Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets

Glass MC, Glass DR, Oliveria JP, et al.
Cell Rep. 2022;39(3): 110728.doi: 10.1016/j. celrep.2022.110728
Regulatory B (Breg) cells are immunosuppressive cells that support immunological tolerance. Through the production of interleukin-10 (IL-10), IL-35, and transforming growth factor β (TGF-β), Breg cells suppress immunopathology by prohibiting the expansion of pathogenic T cells and other pro-inflammatory lymphocytes. In clinical transplantation, Bregs have been linked to operational tolerance, a state in which recipients maintain stable graft function in absence of immunosuppression. In this study, the authors simultaneously quantify cytokine production and immunophenotype in human peripheral B cells across a range of stimulatory conditions and time points using mass cytometry. The analysis shows that multiple functional B cell subsets produce IL-10 and that no phenotype uniquely identifies IL-10+ B cells. Critically, it was observed that a significant portion of IL-10+ B cells co-express the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNFα). However, operationally tolerant liver transplant recipients have a unique enrichment of IL-10+, but not TNFα+ or IL-6+, B cells compared with transplant recipients receiving immunosuppression. Thus, human IL-10-producing B cells constitute an induced, transient state arising from a diversity of B cell subsets that may contribute to maintenance of immune homeostasis. It is critical to note, that in the clinical cohort, transplant controls were on immunosuppression, while graft-tolerant subjects were not, which is an unavoidable limitation in these studies due to standard of care. Likely, the absence of immunosuppression could contribute to some differences in B cell phenotypes and frequencies. Critically, while the results from this analysis suggests CD9 expression and IL-10:TNFα ratios of B cells could serve as biomarkers for allograft tolerance, it remains to be determined if these features are causative or merely correlated.

Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis

Doke T, Abedini A, Aldridge DL, et al.
Nat Immunol. 2022;23(6):947-959. doi:10.1038/s41590-022-01200-7
Kidney fibrosis is the hallmark of end stage kidney disease. The critical improvements observed in short term outcomes in kidney transplantation have not been mirrored by long-tern outcomes. Understanding the mechanisms and cell-specific injury pathways that associate with fibrosis development is critical to prolong the longevity of the graft. Comprehensive genome-wide human kidney tissue transcriptomics identified changes in the expression of many genes in fibrosis. Differentially expressed genes (DEGs) were enriched for metabolism and proximal tubule cell changes, indicating tubule cell dysfunction and loss in fibrosis. As might be expected, inflammation and immune cell response signatures represented the second-largest gene cluster associated with kidney fibrosis. However, a critical knowledge gap remains as the immune cells associated with kidney fibrosis have not been systematically characterized and the trigger for immune cell influx is poorly understood. Consequently, the immune cell interactions that contribute to the initiation and development of fibrotic processes in fibrosis development are not well understood. This is a critical issue in kidney transplantation, where the kidney graft is under continuous alloimmune injury. In this study, using single-cell sequencing to a mouse model of kidney fibrosis, the authors identified a subset of kidney tubule cells with a profibrotic-inflammatory phenotype characterized by the expression of cytokines and chemokines associated with immune cell recruitment. Receptor–ligand interaction analysis and experimental validation indicate that CXCL1 secreted by profibrotic tubules recruits CXCR2+ basophils. In mice, these basophils are an important source of interleukin-6 and recruitment of the TH17 subset of helper T cells. Genetic deletion or antibody-based depletion of basophils results in reduced renal fibrosis. Human kidney single-cell, bulk gene expression and immunostaining validate a function for basophils in patients with kidney fibrosis. The unexpected and important contribution of basophils to renal fibrosis opens new potential therapeutic avenues for the management of kidney fibrosis. Although these studies were done using chronic kidney disease models, they are highly relevant to the evaluation of fibrosis in the kidney graft.

Interleukin 24 promotes cell death in renal epithelial cells and is associated with acute renal injury

Schütte-Nütgen K, Edeling M, Kentrup D, et al.
[published online ahead of print, 2022 Jul 8]. Am J Transplant. 2022;10.1111/ajt.17143. doi:10.1111/ajt.17143
Acute kidney injury is a critical clinical condition associated with a high degree of morbidity and mortality despite the best supportive care in the absence of effective and/or causal treatment. Ischemia-reperfusion injury is one of the main causes of acute kidney injury in renal transplantation. In this manuscript, using a mouse model, the authors found that IL24 is upregulated in the kidney after renal ischemia-reperfusion injury and that tubular epithelial cells and infiltrating inflammatory cells are the source of IL24. Mice lacking IL24 are protected from renal injury and inflammation. Cell culture studies were also used and showed that IL24 induces apoptosis in renal tubular epithelial cells, which is accompanied by an increased endoplasmatic reticulum stress response. Moreover, IL24 induces robust expression of endogenous IL24 in tubular cells, fostering ER-stress and apoptosis. In kidney transplant recipients with delayed graft function and patients at high risk to develop acute kidney injury after cardiac surgery IL24 is upregulated in the kidney and serum. In summary, the study shows for the first time that IL24 is not only a biomarker for acute kidney injury but plays an important mechanistic role involving both extracellular and intracellular targets and pathways. The authors propose that IL24 is a promising new therapeutic target in patients at risk of or with ischemia-induced acute kidney injury

Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients

Hasgur S, Yamamoto Y, Fan R, et al.
Am J Transplant. 2022;22(7):1779-1790. doi:10.1111/ajt.17033
Antibody-mediated lymphoablation is a commonly used therapy in solid organ and stem cell transplantation and autoimmunity. Its efficacy is determined by the balance between the removal of pathogenic lymphocytes and preserving the individual's ability to respond to opportunistic infections. In transplant recipients, T cell reconstitution following lymphoablation is the sum of potentially detrimental homeostatic proliferation of depletion-resistant memory T cells and beneficial thymopoiesis that replenishes non-alloreactive T cells necessary for host protection. Diminishing the extent of homeostatic T cell proliferation is, therefore, essential for improving the efficacy of clinical lymphoablation. The goal of the current study was to identify mediators of B cell activation following lymphoablation in allograft recipients. Transcriptome analysis revealed that macrophage-inducible C-type lectin (Mincle, Clec4e) expression is up-regulated in B cells from heart allograft recipients treated with murine anti-thymocyte globulin (mATG). Recipient Mincle deficiency diminishes B cell production of pro-inflammatory cytokines and impairs T lymphocyte reconstitution. Mixed bone marrow chimeras lacking Mincle only in B lymphocytes have similar defects in T cell recovery. Conversely, treatment with a synthetic Mincle ligand enhances T cell reconstitution after lymphoablation in non-transplanted mice. Treatment with agonistic CD40 mAb facilitates T cell reconstitution in CD4 T cell-depleted, but not in Mincle-deficient, recipients indicating that CD40 signaling induces T cell proliferation via a Mincle-dependent pathway. In summary, this study indicates that following lymphoablation in the settings of transplantation, Mincle is required for recipient B cells to initiate production of proinflammatory cytokines and thus facilitate homeostatic T cell reconstitution. These findings identify Mincle and its endogenous ligands as potential therapeutic targets for minimizing the effects of posttransplant inflammation and improving the efficacy of lymphoablation in transplant recipients.

Transplantation Updates

Transplantation - Week's Most Downloaded Paper

Establishment of Solid Organ Transplantation in the United Arab Emirates #TBT

One of the key unmet areas of medical need in the [United Arab Emirates] was the availability of solid organ transplantation. Collaborative efforts began a few years ago aiming to establish thoracic and abdominal solid organ transplantation from deceased donors in addition to continued development of the existing program in kidney transplantation from living donors. This report summarizes the culmination of those efforts, representing close collaboration between various entities and stakeholders working toward the common goal of enabling citizens and residents of the UAE access to transplant services of the highest quality.

Transplantation Direct - Week's Most Downloaded Paper

Magnetic Resonance Elastography-derived Stiffness Predicts Renal Function Loss and Is Associated With Microvascular Inflammation in Kidney Transplant Recipients #magneticresonance #OpenAccess #TransplantTwitter

Organ stiffening can be caused by inflammation and fibrosis, processes that are common causes of transplant kidney dysfunction. Magnetic resonance elastography (MRE) is a contrast-free, noninvasive imaging modality that measures kidney stiffness. The objective of this study was to assess the ability of MRE to serve as a prognostic factor for renal outcomes.

TTS Needs Assessment Survey

Marcelo Cantarovich
TTS President

The slogan we adopted for the TTS 2022 Congress is "Committed to Access and Transparency" and as a lead-up to the Congress we have launched a new needs assessment survey which will aid TTS in developing new programs, educational material and strategies to better improve access and transparency in the field of transplantation. As a non-governmental organization in official relations with the World Health Organization (WHO) the information collected will feed into the work TTS is doing as part of our WHO collaboration.

Your support, by completing this survey, will contribute to the success of this initiative. Your answers will be kept confidential and anonymous.

The survey will take 6+ minutes and must be done from a computer or tablet.

Women in Transplantation Event

Women in Transplantation at the International Symposium on “Sex and Gender in Organ Transplantation: The Female Perspective”

It is with great pleasure that we hereby announce that the International Symposium on “Sex and Gender in Organ Transplantation: The Female Perspective” will be held from October 5-7, 2022. The symposium will be a hybrid event with the onsite meeting taking place at the Herrenhausen Palace Congress Centre, Hannover, Germany.

The symposium will connect clinicians, researchers and patients from around the globe. The aim is to explore the needs and define the areas for future research. It is organized in close collaboration with the Women in Transplantation (WIT) initiative of The Transplantation Society (TTS) and exclusively funded by the German VolkwagenStiftung. Please find details on the program by visiting our website:

We welcome you to support us by joining our hybrid symposium. You are welcome to submit an abstract of either original research or summarize clinical, research, societal or patient related aspects related to the symposium’s topic. We are able to provide travel grants to a limited number of participants. Please see the website for more details.

If there are any questions, please do not hesitate to contact us. Click the links below for the preliminary program and the template for abstract submission.

Anette Melk, MD PhD
Hannover Medical School
Hannover, Germany
Bethany J. Foster, MD
McGill University
Montreal, Canada
Germaine Wong, MD
University of Sydney
Sydney, Australia
Louise Lerminiaux
Patient advocate
Los Angeles, USA

Clinical Decision Support Tool for Resistant/Refractory CMV in Transplantation

The Transplantation Society (TTS) has participated in the design, review, and beta testing for the CDST. TTS has officially endorsed this clinical decision support tool.

Cytomegalovirus (CMV) is one of the most common viral infections in the post-transplant setting, including solid organ transplant (SOT) and hematopoietic cell transplant (HCT). CMV conveys a high risk of complications including graft loss, morbidity, and mortality. There are currently no FDA approved therapies for CMV after transplantation and those that are currently in use have serious side effects including kidney and bone marrow toxicity. Data from RMEI medical education programs, as well as information gleaned from CMV experts including TTS Education Committee Member, Camille Kotton MD, show that clinicians who treat CMV in transplant patients need guidance regarding which CMV therapies to choose and how to incorporate a new antiviral (maribavir) in clinical practice.

The Resistant/Refractory Cytomegalovirus Clinical Decision Support Tool (CDST) has been built using the algorithm of the Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation by Camille Kotton, MD et al.

ISODP Journal Watch Newsletter

The Transplantation Society (TTS) has participated in the design, review, and beta testing for the CDST. TTS has officially endorsed this clinical decision support tool.

This edition of the Journal Watch focuses mainly on aspects of system development, from how to measure and compare performance metrics to what are the signs of work-related issues we should be monitoring in donor coordinators. There is an analysis of how even similarly structured systems in the UK and Australia can be very difficult to compare using currently collected data. There is also a report from an international round table exploring how donation after voluntary euthanasia (also known as medical assistance in dying) has been integrated into end-of-life care in a few countries and a description of DCD protocol variations in the area covered by an organ donation organization in the United States, and others.

Sonny Dhanani (Associate Director, CDTRP and Chair of the Canadian Donation Physician Network)
Matthew Weiss (Medical Director - Organ Donation at Transplant Québec and National Lead of the LEADDR Research Program, CDTRP)

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