Evidence map›Paper›PMID 39254734›Full record

ReviewIntensive care medicine2024

Complement system activation: bridging physiology, pathophysiology, and therapy.

Elie Azoulay, Julien Zuber, Ahmed Aziz Bousfiha, Yun Long, Ying Tan, Sushan Luo, Meriem Essafti, Djillali Annane

Abstract readReview
PubMed Publisher
In one paragraph

Review in Intensive care medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. SARS-CoV-2 seeds IAPP aggregation and β-cell failure.Signal transduction and targeted therapy · 2026
    Article
  3. Article
  4. The long-lived immune system of centenarians.Nature reviews. Immunology · 2026
    Review
  5. Review
  6. Article
  7. Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema. Part 1: ARDS endotypes, including systemic inflammatory response syndrome and sepsis, with dog and cat examples.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Complement C5 Inhibitor Ameliorates a Case of Dysferlinopathy.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Article
  12. Article
  13. Advances in the lectin pathway in systemic lupus erythematosus: from clinical correlations and mechanisms to targeted interventions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Elie AzoulayIntensive Care Unit, Saint-Louis University Hospital, AP-HP, Paris Cité University, Paris, France. elie.azoulay@aphp.fr.ORCID 0000-0002-8162-1508
Julien ZuberDepartment of Kidney and Metabolic Diseases, Transplantation and Clinical Immunology, Necker University Hospital, AP-HP, Paris, France.
Ahmed Aziz BousfihaDepartment of Pediatric Infectious and Immunological Diseases, IbnRochd University Hospital, Casablanca, Morocco.
Yun LongDepartment of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Ying TanRenal Division, Department of Medicine, Peking University First Hospital, Beijing, PR China.
Sushan LuoDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, PR China.
Meriem EssaftiIntensive Care Department, Mother-Children Center, Mohamed VI University Hospital, Marrakech, Morocco.
Djillali AnnaneDepartment of Intensive Care, Raymond Poincaré Hospital, AP-HP, Garches, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Atypical Hemolytic Uremic SyndromeComplement ActivationComplement Inactivating AgentsCOVID-19Antibodies, Monoclonal, HumanizedComplement System ProteinsHumansMyasthenia GravisSARS-CoV-2Antibodies, Monoclonal, HumanizedComplement Inactivating AgentsComplement System ProteinseculizumabAcute respiratory distress syndromeAtypical hemolytic–uremic syndromeComplement activationComplement system proteinsCritical illnessMyasthenia gravisSepsisSevere COVID-19

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.