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Le Touquet – Paris-Plage, France

Sicard A.,Service de Transplantation Renale Adulte | Sicard A.,University Paris DescartesSorbonne Paris Cite | Amrouche L.,Service de Transplantation Renale Adulte | Amrouche L.,University Paris DescartesSorbonne Paris Cite | And 13 more authors.
American Journal of Transplantation | Year: 2014

The detection of preformed donor-specific alloantibodies (DSA) with multiplex-bead arrays has led to the common observation that individuals without a history of pregnancy, transfusion or transplantation can have circulating anti-HLA antibodies of unknown etiology. We retrospectively analyzed the risk of antibody-mediated rejection (AMR) and graft outcome in 41 kidney transplant recipients with DSA of unknown etiology (DSA cause-unk) at the time of transplantation. Twenty-one patients received a posttransplantation desensitization protocol, and 20 received standard immunosuppressive therapy. The mean number of DSA was 1.4 ± 0.8, ranging from 1 to 5. Complement-dependent cytotoxicity crossmatches were negative for all the patients. Flow cytometry crossmatches were positive in 47.6% of cases. The incidence of acute AMR was 14.6% at 1 year, regardless of the immunosuppressive regimen. No patients experienced graft loss following AMR. At month 12, across the entire population of patients with DSA cause-unk, the outcomes were favorable: the measured glomerular filtration rate was 63.8 ± 16.4 mL/min/1.73 m2, the screening biopsies showed low frequencies of microvascular inflammation and no transplant glomerulopathy, and graft and patient survival were 100%. In conclusion, patients with DSA cause-unk are able to mount AMR but have favorable 1-year outcomes. This study analyzes kidney transplants performed in recipients with preformed donor-specific antibodies but without a history of an HLA-immunizing event, and shows that although these patients may experience antibodymediated rejection, they have a favorable one-year outcome. © 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Ramdani G.,University Paris DescartesSorbonne Paris Cite | Ramdani G.,French Institute of Health and Medical Research | Naissant B.,French Institute of Health and Medical Research | Naissant B.,University Paris DescartesSorbonne Paris Cite | And 20 more authors.
PLoS Pathogens | Year: 2015

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites. © 2015 Ramdani et al.

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