Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

Résumé
Natural killer group 2, member D (NKG2D) is an invariant activatory receptor present on subsets of natural killer and T lymphocytes. It stimulates the cytolytic effector response upon engagement of its various stress-induced ligands NKG2D ligands (NKG2DL). Malignant transformation and conditioning treatment prior to hematopoietic cell transplantation (HCT) are stress factors leading to the activation of the NKG2D/NKG2DL signaling in clinical settings. In the context of HCT, NKG2D-bearing cells can kill both tumor and healthy cells expressing NKG2DL. The NKG2D/NKG2DL engagement has therefore a key role in the regulation of one of the most salient issues in allogeneic HCT, i.e., maintaining a balance between graft-vs.-leukemia effect and graft-vs.-host disease. The present review summarizes the current state of our knowledge pertaining to the role of the NKG2D and NKG2DL in HCT.

Mars 2017 / Frontiers in Immunology – écrit par Carapito R, Aouadi I, Ilias W and Bahram S

Pour plus d’informations :  http://journal.frontiersin.org/article/10.3389/fimmu.2017.00368/full

Transplantation: Desensitization and survival in kidney transplant recipients

Résumé
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.

Mars 2017 / Nature review nephrology – Süsal C, Opelz G

Plus d’informations : https://www.nature.com/articles/nrneph.2017.24

ABO-Incompatible Kidney Transplantation

Résumé
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.

Mots clefs : kidney transplantation, ABO incompatible, survival, desensitization, antibodies

Mars 2017 / Frontier in Immunology – Morath C, Zeier M, Döhler B, Opelz G, Süsal C

Plus d’informations https://www.frontiersin.org/articles/10.3389/fimmu.2017.00234/full

Immune mechanisms of acute and chronic rejection

Résumé

With the currently available immunosuppression, severe T-cell mediated rejection has become a rare event. With the introduction of modern antibody-detection techniques, such as the L-SAB technology, acute or hyperacute antibody-mediated rejection of the kidney are also seen infrequently. In contrast, chronic antibody-mediated rejection is considered to be a major contributor to graft loss in the late posttransplant phase. Problems in the management of chronic antibody-mediated rejection are effective prevention of the development of alloantibodies against donor HLA and the early identification of patients at risk for this entity. Finally, today there is still noeffective strategy to treat this indolent and slowly progressing form of antibody-mediated rejection. Herein, we review the pathomechanisms of the different forms of rejection and the clinical significance of these entities in human kidney transplantation.

Mars 2016 / The Canadian Society of Clinical Chemists – Becker LE, Morath C, Suesal C.

Mots clefs : Antibody; De novo DSA; HLA; Kidney transplantation; Rejection

Plus d’informations
https://www.ncbi.nlm.nih.gov/pubmed/26851348

Clinical relevance of preformed IgG and IgM antibodies against donor endothelial progenitor cells in recipients of living donor kidney grafts

Résumé

Background

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.

Methods

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.

Results

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).

Conclusion

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.

 

Février 2016 / Clinical Transplantation – Daniel V, Sadeghi M, Suesal C, Scherer S, Tran H, Gombos P, Trojan K, Morath C, Opelz G.

Mots clefs : XM-ONE; antibodies against endothelial progenitor cells; graft dysfunction; living donor kidney grafts; preformed EPC antibodies; rejection

Plus d’informations
https://www.ncbi.nlm.nih.gov/pubmed/26537026