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ISN-TTS Webinar: Antibody Mediated Rejection

Antibody-mediated rejection of renal allografts is a main cause of graft loss, that will be the premise of Dr Mengel‘s presentation. No effective treatment protocols have been established, mainly due to challenges in accurate and timely diagnosis and staging of antibody-mediated tissue injury. This presentation will review the current Banff criteria for diagnosing antibody-mediated rejection and discuss the potential for increasing diagnostic accuracy through molecular diagnostic tools. 

Dr Naesens will speak on the histology of Antibody-Mediated Rejection after kidney transplantation and which sometimes is encountered in the absence of HLA-DSA and represents a clinical conundrum. Recent studies shed some light on potential causes, including non-HLA antibodies and direct NK cell activation through missing self. The first presentation of this webinar discusses the clinical presentation, impact and causes of this phenotype of microvascular rejection in the absence of HLA-DSA.

The aim of Dr Lefaucher‘s presentation is to highlight the standard of care and new therapies in AMR and to identify contemporary tools allowing us to evaluate the response to treatment and moving through individualized strategies. With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on small number of prospective randomized trials for the treatment of AMR. 

Dr Böhmig will present antibody-mediated rejection (ABMR) as a leading cause of kidney allograft failure. Its therapy continues to be challenging, and no treatment has been approved for the market thus far. Georg Böhmig will discuss the current level of evidence to support the use of available therapeutic strategies in late/chronic ABMR and the emergence of tailored drugs now being evaluated in systematic clinical trials. Recent systematic trials have questioned the benefits of using the CD20 antibody rituximab or the proteasome inhibitor bortezomib. However, there are now several promising treatment approaches in the pipeline, which are being trialed in phase II and III studies. These include among others interleukin-6 antagonism and CD38-targeting antibodies. New developments will hopefully provide us with effective ways to counteract the deleterious impact of antibody-mediated graft injury. 

Learning Objectives:

1. Standard of care treatment/ TTS treatment guidelines in AMR and ABMR
2. Defining the response to treatment in AMR patients
3. New tools for moving through individualized strategies
4. To review the current Banff criteria for diagnosing antibody-mediated rejection in renal allografts
5. To understand the limitation of histopathology in diagnosing antibody-mediated rejection in renal allografts
6. To discuss emerging molecular diagnostics tool in transplantation pathology
7. Innovative drugs in the pipeline

Further Reading

• Callemeyn et al Kidney Int 2022: Allorecognition and the spectrum of kidney transplant rejection.
  https://doi.org/10.1016/j.kint.2021.11.029
  
• A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology.
  Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, Loupy A, Mengel M, Perkowska-Ptasińska A, Rabant M, Racusen LC, Solez K, Becker JU.Transplantation. 2018 Nov;102(11):1795-1814.
• Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation.
  Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, Dagobert J, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thüsen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RB.Am J Transplant. 2020 Sep;20(9):2305-2317.
• Schinstock et al. Transplantation. 2020 May;104(5):911-922 
• Mayer et al. Curr Opin Organ Transplant. 2021 Feb 1;26(1):97-105