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December 8, 2025Blood

Deep neutrophil phenotyping uncovers complement-mediated neutrophil dysregulation in sickle cell disease

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Authors

WBWilliam BrionesSPSeema R. PatelMSMichelle Long Schoettler

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Overview

Findings reveal complement activation exacerbates neutrophil dysregulation in sickle cell disease during acute chest syndrome, highlighting its role in endothelial damage.

Key Points

  • Investigate the role of complement activation in neutrophil dysregulation during acute chest syndrome in sickle cell disease.
  • Phenotyping blood from SCD patients during ACS and baseline using high-dimensional flow cytometry.
  • Measured complement plasma levels (C3a, C5a, C5b-9) in patients and murine models.
  • Utilized SSC3KO mice to observe complement activation and NET formation.
  • Increased C3 deposition on neutrophils during ACS compared to baseline, with statistical significance.
  • Elevated immature neutrophil levels observed during ACS episodes linked to complement activation.
  • Notable plasma level increases of complement components during ACS indicate a pro-inflammatory state.

Cite This Study

Briones et al. (2025) studied this question.

synapsesocial.com/papers/69362f714fa91c937236e185https://doi.org/10.1182/blood-2025-12
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Also Consider

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

  1. 1Rapidly progressive acute chest syndrome is associated with complement-mediated cell injury in adults with sickle cell disease2025
  2. 2Complement dysregulation during vaso-occlusive episodes can predict development of acute chest syndrome in pediatric patients with sickle cell disease2025
  3. 3Neutrophil-TLR9 is a therapeutic target for acute chest syndrome in sickle cell disease2025
  4. 4Acute chest syndrome (ACS) in sickle cell disease (SCD): pathogenesis and pharmacotherapies in early clinical development2025 · 3 citations
  5. 5C65-12 Clinical and Laboratory Findings in Adults With Sickle Cell Disease Which Increase Risk for Severe Acute Chest Syndrome2026