Léna Absi

Immune-reactive soluble OX40 ligand, soluble CD40 ligand, and interleukin-27 are simultaneously oversecreted in platelet components associated with acute transfusion reactions

Leukoreduction of labile blood components dramatically decreases the frequency of minor, intermediate, and severe adverse events (AEs), referred to as acute transfusion reactions (ATRs), especially after transfusion of platelet components (PCs). The pathophysiology of AEs may result from accumulation of soluble, secreted, platelet (PLT) factors with proinflammatory functions stored in PCs. Thus, several cosynergizing factors associated with PLT accumulation in PCs may contribute to clinically reported ATRs with inflammatory symptoms.

A computerized prediction model of hazardous inflammatory platelet transfusion outcomes.

Background Platelet component (PC) transfusion leads occasionally to inflammatory hazards. Certain BRMs that are secreted by the platelets themselves during storage may have some responsibility. Methodology/Principal Findings First, we identified non-stochastic arrangements of platelet-secreted BRMs in platelet components that led to acute transfusion reactions (ATRs). These data provide formal clinical evidence that platelets generate secretion profiles under both sterile activation and pathological conditions. We next aimed to predict the risk of hazardous outcomes by establishing statistical models based on the associations of BRMs within the incriminated platelet components and using decision trees. We investigated a large (n = 65) series of ATRs after platelet component transfusions reported through a very homogenous system at one university hospital. Herein, we used a combination of clinical observations, ex vivo and in vitro investigations, and mathematical modeling systems. We calculated the statistical association of a large variety (n = 17) of cytokines, chemokines, and physiologically likely factors with acute inflammatory potential in patients presenting with severe hazards. We then generated an accident prediction model that proved to be dependent on the level (amount) of a given cytokine-like platelet product within the indicated component, e.g., soluble CD40-ligand (>289.5 pg/109 platelets), or the presence of another secreted factor (IL-13, >0). We further modeled the risk of the patient presenting either a febrile non-hemolytic transfusion reaction or an atypical allergic transfusion reaction, depending on the amount of the chemokine MIP-1α (<20.4 or >20.4 pg/109 platelets, respectively). Conclusions/Significance This allows the modeling of a policy of risk prevention for severe inflammatory outcomes in PC transfusion.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII–IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09–2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00–1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

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.

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.