Cited by 430Complement system in diseasesBiomarkers in Disease MechanismsCoagulation, Bradykinin, Polyphosphates, and Angioedema

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Complement and Its Receptors: New Insights into Human Disease

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Holers, V. Michael·2014·Annual Review of Immunology

DOI 10.1146/annurev-immunol-032713-120154

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Abstract

Although new activation and regulatory mechanisms are still being identified, the basic architecture of the complement system has been known for decades. Two major roles of complement are to control certain bacterial infections and to promote clearance of apoptotic cells. In addition, although inappropriate complement activation has long been proposed to cause tissue damage in human inflammatory and autoimmune diseases, whether this is indeed true has been uncertain. However, recent studies in humans, especially those using newly available biological therapeutics, have now clearly demonstrated the pathophysiologic importance of the complement system in several rare diseases. Beyond these conditions, recent genetic studies have strongly supported an injurious role for complement in a wide array of human inflammatory, degenerative, and autoimmune diseases. This review includes an overview of complement activation, regulatory, and effector mechanisms. It then focuses on new understandings gained from genetic studies, ex vivo analyses, therapeutic trials, and animal models as well as on new research opportunities.

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Background
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Authors: Holers, V. M.
Affiliations: University of Colorado Anschutz (US)
Corresponding author: Holers, V. Michael
ORCID: Holers, V. Michael
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2014-03-21
Volume: 32
Issue: 1
Pages: 433-459
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-032713-120154
OpenAlex: W2163243965
Cited by: 430
References: 152
Citations by year: 2026: 21 · 2025: 25 · 2024: 33 · 2023: 27 · 2022: 39 · 2021: 48 · 2020: 46 · 2019: 42 · 2018: 34 · 2017: 40 · 2016: 36 · 2015: 27 · 2014: 10
FWCI: 3.68
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Lupus Research Alliance
National Institutes of Health
National Institute of Allergy and Infectious Diseases (R21AI105717)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR051749)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords: complement system, complement receptors, complement activation, complement regulation, efferocytosis, bacterial infection, inflammatory diseases, autoimmune disease, degenerative diseases, rare diseases, genetic research, complement therapeutics, tissue damage
MeSH terms: Animals, Carrier Proteins, Complement System Proteins, Complement Activation, Disease Models, Animal, Disease Susceptibility, Humans, Protein Binding, Receptors, Complement, Signal Transduction, Genetic Predisposition to Disease

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Complement and Its Receptors: New Insights into Human Disease

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