ArticleHaematologica2019
Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets.
Article in Haematologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Design of a modified platelet immunofluorescence test to assess platelet-reactive antibody burden and its association with platelet functional exhaustion and clinical features in chronic immune thrombocytopenia.British journal of haematology · 2026Article
- Clinical application of a modified platelet desialylation test for mechanistic characterization of platelet transfusion refractoriness.Transfusion · 2026Article
- Immune-mediated platelet refractoriness: Mechanisms, diagnostics, and therapeutic breakthroughs.Transfusion medicine (Oxford, England) · 2026Review
- Article
- Alloantibody IgG subclasses have differential activity in clearing transfused platelets in mice.Blood advances · 2026Article
- Anti-HLA class I IgG subclasses skew platelet activation mechanisms in transfusion refractoriness.Haematologica · 2026Article
- Targeting macrophages prevents alloantibody-mediated platelet clearance in a murine model of transfusion refractoriness.Blood advances · 2026Article
- Existence and significance of anti-HLA-C autoantibodies to primary and persistent platelet transfusion refractoriness in patients with hematologic disorders: a retrospective study from a single centre.Annals of medicine · 2025Article
- A homogeneous immunoassay technology based on liposomes and the complement system enables one-step, no-wash, rapid diagnostics directly in serum.Analytical and bioanalytical chemistry · 2025Article
- Article
- Factors affecting IgG4-mediated complement activation.Frontiers in immunology · 2023Article
- Article
- Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects.Frontiers in immunology · 2023Review
- Altered Fc glycosylation of anti-HLA alloantibodies in hemato-oncological patients receiving platelet transfusions.Journal of thrombosis and haemostasis : JTH · 2022Article
- Fc galactosylation of anti-platelet human IgG1 alloantibodies enhances complement activation on platelets.Haematologica · 2022Article
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Precision Engineering of an Anti-HLA-A2 Chimeric Antigen Receptor in Regulatory T Cells for Transplant Immune Tolerance.Frontiers in immunology · 2021Article
- Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation.Blood advances · 2020Article
- Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion.Diseases (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High titers of HLA antibodies are associated with platelet refractoriness, causing poor platelet increments after transfusions in a subset of patients with HLA antibodies. Currently, we do not know the biological mechanisms that explain the variability in clinical responses in HLA alloimmunized patients receiving platelet transfusions. Previously we showed that a subset of anti-HLA IgG-antibodies induces FcγRIIa-dependent platelet activation and enhanced phagocytosis. Here, we investigated whether anti-HLA IgG can induce complement activation on platelets. We found that a subset of anti-HLA IgG induced complement activation via the classical pathway, causing C4b and C3b deposition and formation of the membrane-attack complex. This resulted in permeabilization of platelet membranes and increased calcium influx. Complement activation also caused enhanced α-granule release, as measured by CD62P surface exposure. Blocking studies revealed that platelet activation was caused by FcγRIIa-dependent signaling as well as HLA antibody induced complement activation. Synergistic complement activation employing combinations of monoclonal IgGs suggested that assembly of oligomeric IgG complexes strongly promoted complement activation through binding of IgGs to different antigenic determinants on HLA. In agreement with this, we observed that preventing anti-HLA-IgG hexamer formation using an IgG-Fc:Fc blocking peptide, completely inhibited C3b and C4b deposition. Our results show that HLA antibodies can induce complement activation on platelets including membrane attack complex formation, pore formation and calcium influx. We propose that these events can contribute to fast platelet clearance
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