Guillaume Claisse

Relationship between Mean Fluorescence Intensity and C1q/C3d-fixing capacities of anti-HLA antibodies

BACKGROUND Complement-binding assays are proposed to better stratify the risk of antibody-mediated rejection associated-graft failure. Despite promising clinical results, some have suggested that the MFI of anti-HLA antibodies may influence these tests. METHODS We investigated the impact of Abs MFI reduction, induced by plasmapheresis, on C1q- and C3d-binding assays. Sera provided from 7 sensitized kidney transplant patients were analyzed. RESULTS Four hundreds and thirty-three SABs were analyzed. Before plasmapheresis, when compared to C1q- SABs, C1q+ SABs had a higher median MFI [17397 (IQR: 14851-18794) vs. 2745 (IQR: 1125-6476), p<0.01]. SABs that remained C1q+ after plasmapheresis had a higher median MFI. Regarding the C3d assay, results were strictly comparable. MFI value was a powerful predictor of both C1q and C3d positivity [AUC 0.97 (CI95% 0.95-0.99) and 0.96, (CI95% 0.93-0.98), respectively]. CONCLUSION Our data suggest that both C1q- and C3d-binding assays are intimately linked to the MFI of anti-HLA Abs.

Venovenous haemodiafiltration for the management of dabigatran overdose in intensive care unit

Dabigatran is a direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with non-valvular atrial fibrillation. The procedure to manage dabigatran-associated haemorrhages is not well formalized. Conventional haemodialysis has been evaluated with good results. Patients with dabigatran-associated bleeding may be unstable and convective techniques like venovenous haemodiafiltration (HDF) can be interesting. We report the case of a 74-year-old, critically ill patient with haemorrhagic shock and dabigatran overexposure due to acute kidney injury. He underwent HDF and dabigatran blood concentrations decreased from 325.3 ng/mL to 160.5 ng/mL. We report here key pharmacokinetics parameters (half-life, extraction coefficient, clearance).

Protein A-Based Immunoadsorption Is More Efficient Than Conventional Plasma Exchange to Remove Circulating Anti-HLA Antibodies

We retrospectively evaluated the ability of protein-A immunoadsorption (IA) as compared to that of conventional plasma exchanges (PE) in reducing the mean fluorescence intensity (MFI) of anti-HLA antibodies assessed by the single antigen assay in sensitized renal transplant recipients. Change in MFI of 441 anti-HLA antibodies was measured after 1 single session of IA or after 3 consecutive daily PE sessions. While both strategies were able to significantly lower the amount of anti-HLA antibodies, the relative reduction in MFI was higher after IA as compared to PE (-69 vs. -58%, respectively, p = 0.003). This better efficacy of IA was observed despite a lower total volume of treated plasma (105 ± 6 vs. 160 ± 16 ml/kg after IA and after PE, respectively). Our data suggest a higher efficiency of IA over conventional PE sessions to remove anti-HLA antibodies and call for a larger evaluation of IA to confirm its potential added value in desensitization protocols.

How to Escape the Immune Response: What Tumors Teach to Transplant Physicians/Immunologists.

Recent progress in deciphering the mechanisms underlying the concepts of tumor immunosurveillance and immunoevasion has opened new opportunities for the development of effective antitumor therapies. Transplant physicians and immunologists have much to learn from those direct clinical translations of basic science. The 2016 Beaune Seminar in Transplant research brought together researchers from both fields to explore and discuss significant advances in cancer biology, immunotherapies and their potential impacts for the management of cancer in transplant recipients.