[Organ transplantation]

International audienc

INSUFFISANCE RENALE ET ALLOGREFFE DE MOELLE OSSEUSE (INCIDENCE, FACTEURS DE RISQUE ET PRONOSTIC)

BESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Effets immunomodulateurs et mécanismes d action des cellules souches mésenchymateuses de foie fœtal et de moelle osseuse humaines et de leurs exosomes

La transplantation d organes est considérée comme le meilleur traitement des défaillances au stade terminal de plusieurs organes solides (rein, foie, cœur etc). Son évolution est affectée par des causes immunologiques (épisodes de rejet) et/ou toxiques (iatrogénie des traitements immunosuppresseurs) nécessitant le développement de nouvelles approches pour prévenir efficacement les épisodes de rejet et réduire la toxicité des immunosuppresseurs. Les propriétés immunomodulatrices des cellules souches mésenchymateuses ont déjà été démontrées in vivo et in vitro. Leur mode d action immunomodulateur repose sur des contacts cellulaires et des fractions excrétées. La thérapie cellulaire à base de ces cellules pourrait être une alternative du traitement immunosuppresseur médicamenteux. Néanmoins, elle présente certains risques, dont le plus grave est un développement des tumeurs en raison d instabilités génétiques pouvant survenant lors de l amplification de ces cellules ex vivo. Les exosomes sont des microvésicules sécrétées par toutes les cellules comportant des protéines, des ARN et des lipides et impliquées dans la communication intercellulaire. Notre étude met en évidence une inhibition de la prolifération des lymphocytes T et des Natural Killer en présence des cellules souches mésenchymateuses et de leurs exosomes. 3 protéines à potentiel immunomodulateur pourraient être impliquées dans cette action: galectine-3-binding protéine, thrombospondine-1, coronine-1a.DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Effect of the shipment of cadaveric renal allografts on allograft survival.

International audienceBACKGROUND: Since 1996, the allocation of grafts in France has been based on a hierarchical three-level system: national, regional and local. The objective of this study was to determine whether the shipment of cadaveric kidneys according to these new exchange rules affects allograft outcome in the Eastern region of France. METHODS: This retrospective study analysed all renal transplants performed in the four centres of the French Eastern region during 3 years (1996 to 1998). All patients were followed up until death, return to dialysis, last information date or the end of June 2003. Information regarding the donors, recipients and treatments, as well as patient and graft outcome, was recorded. Factors associated with graft loss were analysed using Cox proportional hazard methods. RESULTS: 542 transplants were analysed, 287 (53%) kidneys were transplanted locally, 229 (42.2%) kidneys coming from exchanges within the region and 26 (4.8%) from another region. There were statistically significant differences between the four centres for donors' and recipient' characteristics and for immunosuppressive treatment, but there was no difference between centres regarding patient survival (94.4% at 5 years), graft survival (83.7% at 5 years) or death-censored graft survival (87.8% at 5 years). Compared to locally transplanted grafts, shipped grafts had significantly better human leukocyte antigen (HLA) matching (2.5 +/- 1.3 versus 2.1 +/- 1.0 matches, P = 0.0005 but a longer cold ischaemia time (23.2 +/- 7.9 versus 19.2 +/- 7.8 h, P < 0.0001). Three independent factors were associated with a reduced graft survival: at least one acute rejection, delayed graft function and a shipped graft. CONCLUSION: The results of this study suggest that the shipment of cadaveric renal allografts in a regional distribution system is associated with better HLA matching but is a significant predictor of graft loss at 5 years. It would be advisable to restrict graft sharing to patients whose access to transplantation is limited, taking special care to avoid any additional factors having a detrimental effect on the outcome

Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene.

International audienceHereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be

Misleading de novo detection of serum anti-HLA-A3 antibodies in kidney recipients having received ATG before transplantation.

International audienceAnti-HLA antibody (Ab) monitoring is essential for the follow-up of transplant patients. However, it can be affected by drugs, especially Ab infused as a conditioning regimen for transplantation. ATG Fresenius, commonly used in this setting, is a polyclonal rabbit Ab raised against the Jurkat human T cell line (HLA-A3, 32; B7, 35). We report here the de novo detection by CDC and flow cytometry (Luminex) of anti-HLA-A3 Ab in the serum of kidney recipients treated with ATG Fresenius. The Ab, of rabbit origin, was detected in every assessable patient (n = 16), with the exception of the HLA-A3 recipients and/or recipients receiving an HLA-A3 graft, before becoming undetectable, at latest, at day 102 after transplantation. It is of major importance that transplantation monitoring laboratories bear in mind the possibility of therapeutic Ab detection when interpreting anti-HLA Ab results

Hyperacute rejection after lung transplantation caused by undetected low-titer anti-HLA antibodies.

International audienceHyperacute rejection is an early complication of transplantation, caused by the presence in the recipient of pre-formed donor-directed antibodies (Ab). We report a case of fatal early graft dysfunction after lung transplantation in a female recipient with no anti-HLA Ab detected before transplantation. Further immunologic studies revealed the presence, in the pre-transplant serum, of low-titer anti-HLA Ab directed against the donor's HLA, detectable only by flow-cytometry screening for panel-reactive antibodies. This observation emphasizes the importance of sensitive Ab detection in patients awaiting lung transplantation. Women should be specifically targeted for such sensitive Ab detection

Changing Kidney Allocation Policy in France: the Value of Simulation

This paper advocates the value of simulation to promote changes in kidney allocation. Due to the scarcity of organs and to the competition between transplantation centers to obtain the best organs for their patients, any change in organ allocation policy remains a sensitive issue in public health decision-making. Organ allocation is not easily available for prospective experimental study. Observational studies only support limited changes. A simulation tool in this context permits the comparison of observed results against simulated ones. In our experience in France, it has shown to be a helpful tool during the allocation design phase providing objective facts for the debates and increasing the potential for change