ArticleJournal of hematology & oncology2017
Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- PNH extravascular hemolysis: exploring clinical significance.Blood advances · 2026Article
- Insights in bone marrow failure syndromes: take home messages from the 3rd ESH-EBMT-EHA-IPIG translational research conference.Bone marrow transplantation · 2025Article
- Advances in Complement Inhibition Therapies for Paroxysmal Nocturnal Hemoglobinuria and Autoimmune Hemolytic Disorders.Journal of blood medicine · 2025Review
- CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.Blood advances · 2024Article
- Understanding pharmacological complement inhibition in paroxysmal nocturnal hemoglobinuria.Haematologica · 2024Article
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Low Rate of Clinically Evident Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with a Complement C5 Inhibitor: Results from a Large, Multicenter, US Real-World Study.Journal of blood medicine · 2022Article
- Frequency and perturbations of various peripheral blood cell populations before and after eculizumab treatment in paroxysmal nocturnal hemoglobinuria.Blood cells, molecules & diseases · 2021Article
- Properdin Is a Key Player in Lysis of Red Blood Cells and Complement Activation on Endothelial Cells in Hemolytic Anemias Caused by Complement Dysregulation.Frontiers in immunology · 2020Article
- Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab.Clinical pharmacokinetics · 2019Review
- Small-molecule factor B inhibitor for the treatment of complement-mediated diseases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Different Levels of Incomplete Terminal Pathway Inhibition by Eculizumab and the Clinical Response of PNH Patients.Frontiers in immunology · 2019Article
- Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT.Frontiers in immunology · 2019Review
- Antibody Inhibition of Properdin Prevents Complement-Mediated Intravascular and Extravascular Hemolysis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Signaling of the Complement Cleavage Product Anaphylatoxin C5a Through C5aR (CD88) Contributes to Pharmacological Hematopoietic Stem Cell Mobilization.Stem cell reviews and reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundC5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding.
methodsTo investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway.
resultsWhen RBCs from untreated patients were exposed in vitro to activated complement in the context of C5-blockade, there was the prompt appearance of a distinct C3+ PNH RBC population whose size increased with time and also with the rate of complement activation. Eventually, all PNH RBCs become C3+ to the same extent, without differences between old and young (reticulocytes) PNH RBCs.
conclusionsThis study indicates that the distinct (C3+ and C3-) PNH RBC populations are not intrinsically different; rather, they result from a stochastic all-or-nothing phenomenon linked to the time-dependent cumulative probability of each individual PNH red cell to be exposed to levels of complement activation able to trigger C3 binding. These findings may envision novel approaches to reduce C3 opsonization and the subsequent extravascular hemolysis in PNH patients on eculizumab.
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