Abstract
Elimination of donor-specific antibodies against HLA has been used to enable transplantation of HLA-incompatible kidneys from living donors. In contrast to two previous US studies, a UK study now reports that desensitization does not offer a survival benefit over remaining on the waitlist for a compatible organ.
March 2017 / Nature review nephrology – Süsal C, Opelz G
More informations: https://www.nature.com/articles/nrneph.2017.24
Abstract
ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes.
Keywords: kidney transplantation, ABO incompatible, survival, desensitization, antibodies
March 2017 / Frontier in Immunology – Morath C, Zeier M, Döhler B, Opelz G, Süsal C
More informations: https://www.frontiersin.org/articles/10.3389/fimmu.2017.00234/full
Credit: interpharma
An article from Sara Käch with Professor Claudia Lengerke, Basel, Newsroom Interpharma, March 2017
The central point for succeeding a transplant is for the organ not to be rejected. A research project with Basel is developing a new diagnostic tool to help reducing transplant rejection process. The project “Tridiag – New diagnostic tools in transplantation medicine” brings together researchers from Basel, Freiburg, Heidelberg, Mainz and Strasbourg. Their common goal: prevent kidney transplant rejection and graft-versus-host disease in hematopoietic stem cell transplantation for a longer life expectancy. Specific genetic markers have to match between the donor and the recipient in order for the transplanted organ not to be rejected or the transplanted cells to consider the recipient as ”non-self” (graft-versus-host disease).
These past few years, scientists discovered a protein named MICA, which has an important role in the graft rejection: if donor and recipient have the same version (allele) of the MICA protein, rejection is 20% lower than when the version is different.
Why is MICA so important for the success of a transplant? “MICA belongs to the group of MHC proteins (Major Histocompatibility Complex). Thanks to this protein group, immune cells can recognize foreign (non-self) structures in human cells and eradicate them. These foreign structures come from infections or degeneration but also when donor and recipient of an organ transplant are too different. The expression of MHC (and MICA) in the donor cells in comparison with the one from the recipient indicate therefore in a very significant way the rate of rejection potential.” Explains Claudia Lengerke, Professor and researcher in the field of hematology and stem cells at the University of Basel and Head physician at the University Hospital of Basel.
The purpose of the cooperation project is to identify how much the variation of MICA between the donor and the recipient and the anti-MICA antibodies in their blood can enable to provide in a reliable way for the success of the transplants. “In Basel, our project is to focus on the analysis of patients who become hematopoietic stem” says Claudia Lengerke. “We look for the relevant prognostic of the anti-MICA antibodies in the serum and the genetic differences in the MICA molecules. What is of interest for us, is to know how such differences affect the future transplant rejection and the graft-versus-host disease.”
The basel researcher points the fact that MICA is not the only protein which impacts rejection. Moreover, there is not always a perfectly matched donor available for each patient needing a transplant. “We expect that the results of this project will enable to lower the percentage of rejection and graft-versus-host disease for at least some patients and will improve their survival rate.”
Original article: http://newsroom.interpharma.ch/2017-03-08-abstossung-voraussehen
Amphithéâtre – FORUM – Faculté de médecine
4 rue Kirschleger / 67000 Strasbourg
For any question, please contact Caroline Debien, project manager: tridiag@unistra.fr /+33 (0)3 68 85 39 85
Abstract
Literature reports suggest that non-HLA-antibodies against human endothelial progenitor cells (EPC) can be detected in pre-transplant recipient serum and that EPC antibodies can have a deleterious influence on the graft.
We investigated 71 renal transplant recipients from living donors for a possible influence of pre-transplant donor-specific IgG and/or IgM recipient antibodies against EPC of the donor using the flow cytometric XM-ONE cross-match.
Eight of the 71 patients developed acute biopsy-proven rejection. Two of these patients showed IgM antibodies against EPC prior to transplantation while the other six patients had neither IgG nor IgM EPC antibodies. Conversely, pre-transplant IgG or IgM antibodies against EPC were detected in 19 patients without acute rejection (3 × both IgG and IgM, 1 × IgG and 15 × IgM). The remaining 44 patients had neither EPC antibodies nor experienced rejection. Comparing serum creatinine levels at one month and one yr post-transplant within and among the three patient groups revealed that serum creatinine levels were similar in patients with or without EPC antibodies (p > 0.05).
In this series of 71 recipients with living donor kidneys, pre-transplant EPC antibodies detected with the XM-ONE test kit were neither associated with acute rejection nor with graft function at one month or one yr.
February 2016 / Clinical Transplantation – Daniel V, Sadeghi M, Suesal C, Scherer S, Tran H, Gombos P, Trojan K, Morath C, Opelz G.
Keywords: XM-ONE; antibodies against endothelial progenitor cells; graft dysfunction; living donor kidney grafts; preformed EPC antibodies; rejection
More informations: https://www.ncbi.nlm.nih.gov/pubmed/26537026
