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Updated: Jun 13, 2025
Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
Published on: June 15, 2019
Complement system activation: bridging physiology, pathophysiology, and therapy
Elie Azoulay1, Julien Zuber2, Ahmed Aziz Bousfiha3,4,5
1Intensive Care Unit, Saint-Louis University Hospital, AP-HP, Paris Cité University, Paris, France. elie.azoulay@aphp.fr.
Insights
The complement system is vital for immunity but overactivation causes disease. Effective inhibitors exist for conditions like atypical hemolytic uremic syndrome and myasthenia gravis, though more research is needed.
Area of Science:
- Immunology
- Molecular Biology
- Pathophysiology
Background:
- The complement system, comprising over 50 proteins, is integral to innate immunity, involving a proteolytic cascade.
- Dysregulation of complement system activation is pathogenic in diseases like sepsis and acute respiratory distress syndrome.
- Excessive complement activation contributes to tissue damage, inflammation, and capillary leakage, potentially worsening severe COVID-19.
Purpose of the Study:
- To review the normal complement system and its dysregulation in critical illnesses.
- To discuss complement overactivation in atypical hemolytic uremic syndrome (aHUS) and myasthenia gravis.
- To highlight the efficacy and challenges of complement-inhibiting therapies.
Main Methods:
- Review of scientific literature on complement system function and dysregulation.
- Analysis of the role of complement in critical illnesses and specific autoimmune diseases.
- Discussion of diagnostic approaches and therapeutic strategies, including complement inhibitors.
Main Results:
- Complement overactivation is implicated in sepsis, ARDS, severe COVID-19, aHUS, and myasthenia gravis.
- Early complement inhibition is effective, with eculizumab and ravulizumab being key therapies.
- Prophylactic use of complement inhibitors can prevent aHUS recurrence post-transplantation.
Conclusions:
- The complement system is essential but its overactivation causes significant disease.
- Effective complement inhibitors are available, but optimal use and personalized treatment require further investigation.
- Advanced diagnostics and treatment markers are needed for better complement-mediated disease management.
Abstract:
The complement system is a set of over 50 proteins that constitutes an essential part of the innate immune system. Complement system activation involves an organized proteolytic cascade. Overactivation of complement system activation is the main pathogenic mechanism of several diseases and contributes to the manifestations of many other conditions. This review describes the normal complement system and the role for complement dysregulation in critical illnesses, notably sepsis and acute respiratory distress syndrome. Complement activation is involved in the immune system response to pathogens but, when excessive, can contribute to tissue damage, runaway inflammation, and capillary leakage syndrome. Complement overactivation may play a key role in severe forms of coronavirus disease 2019 (COVID-19). Two diseases whose manifestations are mainly caused by complement overactivation, namely, atypical hemolytic and uremic syndrome (aHUS) and myasthenia gravis, are discussed. A diagnostic algorithm for aHUS is provided. Early complement-inhibiting therapy has been proven effective. When renal transplantation is required, complement-inhibiting drugs can be used prophylactically to prevent aHUS recurrence. Similarly, acetylcholine-receptor autoantibody-positive generalized myasthenia gravis involves complement system overactivation and responds to complement inhibition. The two main complement inhibitors used in to date routine are eculizumab and ravulizumab. The main adverse event is Neisseria infection, which is rare and preventable, but can be fatal. The complement system is crucial to health but, when overactivated, can cause or contribute to disease. Effective complement inhibitors are now available, although additional data are required to determine optimal regimens. Further research is also needed to better understand the complement system, develop advanced diagnostic tools, and identify markers that allow the personalization of treatment strategies.
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