ArticleHaematologica2015
Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies.
Article in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04024202 (The DRAIHA Study), which is not on this map. Cited by 20 papers.
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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.
The DRAIHA Study: Data Registry of AutoImmune Hemolytic Anemia, to Improve Diagnostic Testing for the Development of Personalized Treatment Protocols in AIHA Patients
Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- C1-inhibitor treatment in patients with severe complement-mediated autoimmune hemolytic anemia.Blood advances · 2023Trial
- [Clinical characteristics and prognosis of patients with direct antiglobulin test-negative autoimmune hemolytic anemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- Host immune dysfunction and Mycoplasma pneumoniae immune evasion: dual drivers of pathogenesis in Mycoplasma pneumoniae pneumonia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Case Report: Severe mixed autoimmune hemolytic anemia associated with acute cytomegalovirus infection in an immunocompetent adult.Frontiers in immunology · 2026Article
- Exploring Protein A Immunoadsorption for Autoimmune Hemolytic Anemia with Hyper-IgG4emia.The American journal of case reports · 2025Article
- Cold-antibody Autoimmune Hemolytic Anemia: its Association with Neoplastic Disease and Impact on Therapy.Current oncology reports · 2024Review
- Management of autoimmune haemolytic anaemia in low-to-middle income countries: current challenges and the way forward.The Lancet regional health. Southeast Asia · 2024Review
- The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?Frontiers in immunology · 2023Review
- The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation.Clinical & translational immunology · 2023Article
- Warm autoimmune haemolytic anaemia seen in association with primary sclerosing cholangitis in the setting ofBMJ case reports · 2022Article
- Thromboembolic complications in autoimmune hemolytic anemia: Retrospective study.European journal of haematology · 2022Article
- Halting targeted and collateral damage to red blood cells by the complement system.Seminars in immunopathology · 2021Review
- Efficacy of eculizumab in refractory life-threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia.Clinical case reports · 2020Article
- Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells.Haematologica · 2020Article
- New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia.Frontiers in immunology · 2020Review
- C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Novel insights into the treatment of complement-mediated hemolytic anemias.Therapeutic advances in hematology · 2019Review
- Complement Deposition and IgG Binding on Stored Red Blood Cells Are Independent of Storage Time.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2018Article
- Irregular antibodies in no hemolytic autoimmune diseases are able to induce erythrophagocytosis.Immunologic research · 2017Article
- Management of refractory autoimmune hemolytic anemia via allogeneic stem cell transplantation.Bone marrow transplantation · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient's erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients' sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients' sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients' erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.