Régulation de la fonction lymphocytaire T allogénique par la molécule HLA-G et son implication en transplantation

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

MORTALITE ET FREQUENCE DES REJETS AU COURS DES TRANSPLANTATIONS COMBINEES HEPATIQUES ET RENALES

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les lymphomes cérébraux primitifs après transplantation rénale (analyse rétrospective)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The cannabinoid receptor 1 is involved in renal fibrosis during chronic allograft dysfunction: Proof of concept

International audienceChronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney-transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post-transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus-mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology

In vivo gene targeting of IL-3 into immature hematopoietic cells through CD117 receptor mediated antibody gene delivery.

BACKGROUND: Targeted gene transfection remains a crucial issue to permit the real development of genetic therapy. As such, in vivo targeted transfection of specific subsets of hematopoietic stem cells might help to sustain hematopoietic recovery from bone marrow aplasia by providing local production of growth factors. METHODS: Balb/C mice were injected intravenously, with an anti-mouse c-kit (CD117) monoclonal antibody chemically coupled to a human IL-3 gene-containing plasmid DNA. Mice were sacrificed for tissue analyses at various days after injection of the conjugates. RESULTS: By ELISA, the production of human IL-3 was evidenced in the sera of animals 5 days after treatment. Cytofluorometric analysis after in vivo transfection of a reporter gene eGFP demonstrated transfection of CD117+/Sca1+ hematopoietic immature cells. By PCR analysis of genomic DNA and RNA using primer specific pIL3 sequences, presence and expression of the human IL-3-transgene were detected in the bone marrow up to 10 days in transfected mice but not in control animals. CONCLUSIONS: These data clearly indicate that antibody-mediated endocytosis gene transfer allows the expression of the IL-3 transgene into hematopoietic immature cells, in vivo. While availability of marketed recombinant growth factors is restricted, this targeting strategy should permit delivery of therapeutic genes to tissues of interest through systemic delivery. In particular, the ability to specifically target growth factor expression into repopulating hematopoietic stem cells may create new opportunities for the treatment of primary or radiation-induced marrow failures

A Randomized Prospective Study Comparing Anti–T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients

International audienceBackground:Two prospective studies that were performed before the era of highly sensitive solid-phaseassays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patientsgiven polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies.Methods:This prospective pilot randomized French multicenter study aimed to compare anti–T-lympho-cyte Ig (ATLG) (n¼32) and basiliximab (n¼27) in highly sensitized kidney-transplant patients withoutpreformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigenflow bead assay.Only patients with a calculated panel reactive antibody$50$5000 and without a historical pDSA and without a pDSA on the day of trans-plantation were included.Results:Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss,and death was observed in 18.8% (95% confidence interval [CI], 8.9%–37.1%) and 18.8% (95% CI, 8.9%–37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%–34.8%) and 28.2% (95% CI, 14.2%–51.2%) ofpatients who received basiliximab, respectively at 6 (P¼0.66) and 12 (P¼0.62) months post-transplantation.One T cell–mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediatedrejection due to ade novodonor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%).Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups.Conclusion:This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs,both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power,these results should be interpreted with cautio

ABO Blood Group Incompatibility Protects Against SARS-CoV-2 Transmission

International audienceABO blood groups appear to be associated with the risk of SARS-CoV-2 infection, but the underlying mechanisms and their real importance remain unclear. Two hypotheses have been proposed: ABO compatibility-dependence (neutralization by anti-ABO antibodies) and ABO-dependent intrinsic susceptibility (spike protein attachment to histo-blood group glycans). We tested the first hypothesis through an anonymous questionnaire addressed to hospital staff members. We estimated symptomatic secondary attack rates (SAR) for 333 index cases according to spouse ABO blood group compatibility. Incompatibility was associated with a lower SAR (28% vs. 47%; OR 0.43, 95% CI 0.27–0.69), but no ABO dependence was detected in compatible situations. For the second hypothesis, we detected no binding of recombinant SARS-CoV-2 RBD to blood group-containing glycans. Thus, although no intrinsic differences in susceptibility according to ABO blood type were detected, ABO incompatibility strongly decreased the risk of COVID-19 transmission, suggesting that anti-ABO antibodies contribute to virus neutralization