Trial reportHaematologica2014
Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria.
Trial report in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti-C5 therapy.HemaSphere · 2026Article
- PNH extravascular hemolysis: exploring clinical significance.Blood advances · 2026Article
- C3 mutations and poor pegcetacoplan response in paroxysmal nocturnal hemoglobinuria.Frontiers in immunology · 2025Article
- Changes in Hematologic Lab Measures Observed in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors, Ravulizumab and Eculizumab: Real-World Evidence from a US Based EMR Network.Hematology reports · 2023Article
- Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases.Immunological reviews · 2023Review
- Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations.Journal of blood medicine · 2023Review
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective.Journal of blood medicine · 2022Review
- Halting targeted and collateral damage to red blood cells by the complement system.Seminars in immunopathology · 2021Review
- Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.Progress in retinal and eye research · 2021Review
- Complement Inhibition for the Treatment of Myasthenia Gravis.ImmunoTargets and therapy · 2020Review
- Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease.Frontiers in immunology · 2020Review
- 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
- Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of "Fogo Selvagem" Pemphigus Foliaceus.Frontiers in immunology · 2019Article
- Different Levels of Incomplete Terminal Pathway Inhibition by Eculizumab and the Clinical Response of PNH Patients.Frontiers in immunology · 2019Article
- Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria.Seminars in hematology · 2018Review
- Diseases of complement dysregulation-an overview.Seminars in immunopathology · 2018Review
- Complement in cancer: untangling an intricate relationship.Nature reviews. Immunology · 2018Review
- Complementopathies.Blood reviews · 2017Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement blockade by eculizumab is clinically effective in hemolytic paroxysmal nocturnal hemoglobinuria. However, the response is variable and some patients remain dependent on red blood cell transfusions. In 72 patients with hemolytic paroxysmal nocturnal hemoglobinuria on eculizumab we tested the hypothesis that response may depend on genetic polymorphisms of complement-related genes. We found no correlation between the complement component C3 genotypes and the need for blood transfusions. On the other hand, we found a significant correlation with the HindIII polymorphism of a complement regulatory gene, the complement receptor 1 (CR1) gene. At this locus two co-dominant alleles are known, of which H (common) is associated with high expression, whereas L (rare) is associated with low expression of CR1 on red blood cells. Patients who still needed blood transfusion on eculizumab accounted for 18% of the H/H homozygotes, 33% of the H/L heterozygotes and 68% of the L/L homozygotes (P=0.016). Thus, patients with paroxysmal nocturnal hemoglobinuria who have the L/L genotype are seven times more likely to be sub-optimal responders to eculizumab. Both in vitro and in vivo we found that the CR1 HindIII genotype correlates with the abundance of paroxysmal nocturnal hemoglobinuria red cells that have bound C3, and with the kinetics of C3 binding. These results are consistent with the notion that by affecting C3 binding the CR1 genotype influences the response to eculizumab treatment, and this emerges as a novel example of pharmacogenetics.
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