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December 8, 2025Blood

Patient-derived monoclonal anti-HPA-1a can induce platetet activation through fcyriia

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Authors

JOJanita J. OosterhoffRKRick KapurRVRemco Visser

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Overview

Novel anti-HPA-1a antibody M-204 triggers platelet activation in fetal and neonatal alloimmune thrombocytopenia, suggesting complex pathogenic mechanisms.

Key Points

  • This research aims to characterize the structural and functional diversity of anti-HPA-1a antibodies in FNAIT.
  • Characterized anti-HPA-1a antibodies D-204 and M-204 from a severe FNAIT patient.
  • Assessed binding profiles using flow cytometry on HEK-293F cells and platelets.
  • Investigated platelet aggregation triggered by M-204 using light transmission aggregometry and various antibody formats.
  • M-204 induced platelet aggregation through an FcγRIIa-dependent pathway.
  • Structural modelling revealed unique binding orientation of M-204 compared to D-204.
  • M-204's Fab glycan was confirmed to not interfere with antigen binding or activity.

Cite This Study

Oosterhoff et al. (2025) studied this question.

synapsesocial.com/papers/69362f694fa91c937236df22https://doi.org/10.1182/blood-2025-3019
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Generation of human antibodies targeting human platelet antigen (<scp>HPA)</scp>‐1a2024
  2. 2Structural Basis of HPA-1a Alloimmunization in FNAIT and Allosteric Regulation of Integrin Conformation2026
  3. 3Maternal anti-HPA-1a antibodies block αIIbβ3 and αvβ3 integrin activation which correlates with FNAIT disease severity2026 · 2 citations
  4. 4HPA-1a antibodies in FNAIT do not distinguish αvβ3 from αIIbβ3 and bind inactive integrins more strongly than active integrins.2025
  5. 5Anti‐ <scp>HPA</scp> ‐1a <scp>IgG3</scp> subclass antibodies induce strong platelet phagocytosis2026