Treatment of atypical hemolytic uremic syndrome (aHUS) by the complement C5 inhibitor eculizumab (Soliris®) is highly effective but unfortunately, associated with an economic pressure on the health care systems even in high incomes countries. Despite spacing infusions having been proposed as the unique solution to minimize this economic impact, no reliable laboratory assays are available to tailor such therapy optimization. We aimed to propose and evaluate a complement composite marker for eculizumab efficacy monitoring in aHUS. We have retrospectively analyzed complement profiles data of eight aHUS patients under eculizumab from the International Registry of HUS/Thrombotic Thrombocytopenia Purpura, and calculated a novel marker "C3:CH ratio" by dividing C3 value by CH one for each sample during induction and maintenance periods. The results significance was compared to the currently used biomarkers for eculizumab tailoring. In contrast to the current biomarkers used for eculizumab efficacy monitoring like CH and soluble or deposit membrane attack complexes, "C3:CH ratio" seems to be the most interesting one since its value at pre-eculizumab dosage equaled 0.92 ± 0.2 while the post-eculizumab one increased significantly to reach 24.54 ± 10.7; P < 0.001. Furthermore, this ratio correlated negatively with platelets count (r = -0.722, P = 0.018) while no correlation was found within the thrombotic microangiopathy (TMA) biomarkers and complement blockade for the other parameters that change in pre and post-eculizumab therapy. As far as we know, this is the first study that suggests a post-eculizumab parameter correlating simultaneously with drug's activity (complement inhibition) and disease activity (platelets counts). Nonetheless, the limited number of patients enrolled in this study should be considered in larger studies to guide eculizumab optimization by indicating the time when subsequent withdrawal or infusion spacing is allowed or recommended.

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Ascorbate pro-drug theory promising possible effective and nontoxic treatment is intensively examined and centered on the importance of both extracellular and intra-cellular effects of ascorbate. In this study, we sought to determine the in vitro cell responsiveness in a plasma free milieu with or without an extracellular catalyst and/or hydrogen peroxide. This project brought to light how ascorbic acid would react to in a Red Blood Cell (RBC) suspension by using the two anti-oxidant pathways. We demonstrated that while ascorbate doesn't require an extracellular metal catalyst to induce cell damage via the lipid peroxidation pathway, the protein-centered metal pathway could be enhanced by a divalent cation, hydrogen peroxide or both. The current lack of understanding of ascorbate potential mechanism excites us to propose some insights for the vitamine C pharmacologic dose pro-oxidant activity.