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<p>Acute hypoxia triggers multiple physiological and immune responses, yet the immediate systemic effects on circulating complement proteins remain insufficiently characterized. The complement cascade plays a central role in inflammation, host defense, and ischemia-related tissue injury, but its regulation during transient oxygen deprivation and reoxygenation in humans is poorly understood. Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0, 2, 4, and 6&#xa0;km (pO₂ = 9.64&#xa0;kPa) followed by reoxygenation under normoxic conditions. Blood samples were collected at baseline, peak hypoxia (6&#xa0;km), and after reoxygenation. Quantitative plasma proteomics was performed using targeted multiple-reaction-monitoring mass spectrometry to quantify key complement components (C1 complex, C3–C9, factor B) in 16 participants with complete datasets. Hematological parameters were analyzed in parallel. Hypoxia transiently increased leukocyte and platelet count, whereas hematocrit and mean corpuscular volume slightly decreased. While only slightly increasing during hypoxia, most complement peptides - including C1S, C1R, C3, C5, C7, C9, and CFAB - showed a coordinated reduction in relative abundance upon reoxygenation compared to both baseline and hypoxia (median fold-change ≈ 0.6–0.8; <i>p</i> &lt; 0.05). Correlation analysis revealed coherent clustering among complement components but only weak associations with hematological indices. Acute hypoxia elicits rapid and reversible changes in the circulating complement peptide pool in healthy humans. Targeted plasma proteomics demonstrates clear oxygen-phase–dependent dynamics, with a coordinated decrease after reoxygenation. This pattern is consistent with reduced circulating availability of complement components, activation-associated consumption, and/or redistribution within the intravascular compartment. Future validation of these findings in certain patient cohorts may define translational relevance and functional consequences.</p> Graphical abstract <p>Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0&#xa0;km, 2&#xa0;km, 4&#xa0;km, and 6&#xa0;km. Hypoxia increased plasma concentrations of several proteins of the complement system as analyzed by quantitative mass spectrometry. Upon reoxygenation, most complement peptides decreased to or below baseline.</p>

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Oxygen-dependent modulation of the human complement system during acute normobaric hypoxia: a translational plasma proteomics study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月21日

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  • Alexander Lang,
  • Tin Yau Pang,
  • Sarah Piel,
  • Daniel Oehler,
  • Elric Zweck,
  • Khatereh Shahrjerdi,
  • Madlen Okkasian,
  • Jacqueline Georgy,
  • Yvonne Reinders,
  • Ashley-Jane Duplessis,
  • Jens Tank,
  • Jens Jordan,
  • Susanne Pfeiler,
  • Albert Sickmann,
  • Malte Kelm,
  • Christian Jung,
  • Norbert Gerdes

摘要

Acute hypoxia triggers multiple physiological and immune responses, yet the immediate systemic effects on circulating complement proteins remain insufficiently characterized. The complement cascade plays a central role in inflammation, host defense, and ischemia-related tissue injury, but its regulation during transient oxygen deprivation and reoxygenation in humans is poorly understood. Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0, 2, 4, and 6 km (pO₂ = 9.64 kPa) followed by reoxygenation under normoxic conditions. Blood samples were collected at baseline, peak hypoxia (6 km), and after reoxygenation. Quantitative plasma proteomics was performed using targeted multiple-reaction-monitoring mass spectrometry to quantify key complement components (C1 complex, C3–C9, factor B) in 16 participants with complete datasets. Hematological parameters were analyzed in parallel. Hypoxia transiently increased leukocyte and platelet count, whereas hematocrit and mean corpuscular volume slightly decreased. While only slightly increasing during hypoxia, most complement peptides - including C1S, C1R, C3, C5, C7, C9, and CFAB - showed a coordinated reduction in relative abundance upon reoxygenation compared to both baseline and hypoxia (median fold-change ≈ 0.6–0.8; p < 0.05). Correlation analysis revealed coherent clustering among complement components but only weak associations with hematological indices. Acute hypoxia elicits rapid and reversible changes in the circulating complement peptide pool in healthy humans. Targeted plasma proteomics demonstrates clear oxygen-phase–dependent dynamics, with a coordinated decrease after reoxygenation. This pattern is consistent with reduced circulating availability of complement components, activation-associated consumption, and/or redistribution within the intravascular compartment. Future validation of these findings in certain patient cohorts may define translational relevance and functional consequences.

Graphical abstract

Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0 km, 2 km, 4 km, and 6 km. Hypoxia increased plasma concentrations of several proteins of the complement system as analyzed by quantitative mass spectrometry. Upon reoxygenation, most complement peptides decreased to or below baseline.