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Complement system in diseases
Research Guide
What is Complement system in diseases?
The complement system in diseases refers to the involvement of the complement cascade—a key component of innate immunity—in the pathogenesis, regulation, and treatment of various disorders including thrombotic microangiopathies, hemolytic uremic syndrome, age-related macular degeneration, schizophrenia, and inflammatory conditions.
Research on the complement system in diseases encompasses 50,054 works that examine its roles in immune surveillance, homeostasis, and pathological dysregulation. Studies highlight genetic variants such as complement factor H polymorphisms linked to age-related macular degeneration (AMD) and complement component 4 variations associated with schizophrenia risk. Therapeutic strategies like Eculizumab and therapeutic apheresis target complement overactivation in conditions such as thrombotic microangiopathies and glomerular diseases.
Topic Hierarchy
Research Sub-Topics
Complement Factor H in Diseases
This sub-topic investigates CFH polymorphisms, regulation, and roles in age-related macular degeneration and atypical HUS. Researchers study structure-function relationships and therapeutic targeting.
Complement in Thrombotic Microangiopathies
This sub-topic covers alternative pathway dysregulation in aHUS, C3 glomerulopathy, and TMA pathogenesis. Researchers analyze genetic variants and biomarkers for diagnosis and monitoring.
Eculizumab Therapy in Complement Disorders
This sub-topic evaluates C5 inhibitor efficacy, resistance mechanisms, and long-term outcomes in PNH, aHUS, and gMG. Researchers develop next-generation complement inhibitors.
Complement Regulation and Homeostasis
This sub-topic examines membrane cofactors, soluble regulators, and feedback loops maintaining immune balance. Researchers model amplification control in inflammation and infection.
Complement Genetics
This sub-topic maps rare variants and copy number variations in complement genes across diseases like AMD, schizophrenia, and COVID-19 severity. Researchers perform GWAS and functional genomics.
Why It Matters
Dysregulation of the complement system contributes to microvascular injury and thrombosis in severe COVID-19, as shown in five cases with complement-associated damage reported by Magro et al. (2020) in "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases". In AMD, a common variant in complement factor H increases risk, with Klein et al. (2005) identifying it in a genome-wide screen of 96 cases and 50 controls in "Complement Factor H Polymorphism in Age-Related Macular Degeneration". Guidelines from Rovin et al. (2021) in "KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases" recommend complement inhibitors like Eculizumab for managing glomerular diseases involving complement activation. Padmanabhan et al. (2019) in "Guidelines on the Use of Therapeutic Apheresis in Clinical Practice
Reading Guide
Where to Start
"Complement: a key system for immune surveillance and homeostasis" by Ricklin et al. (2010), as it provides a foundational overview of complement's physiologic roles before diving into disease-specific papers.
Key Papers Explained
Ricklin et al. (2010) in "Complement: a key system for immune surveillance and homeostasis" establishes complement's immune functions, which Klein et al. (2005) and Edwards et al. (2005) in "Complement Factor H Polymorphism in Age-Related Macular Degeneration" and "Complement Factor H Polymorphism and Age-Related Macular Degeneration" extend to AMD genetics. Sekar et al. (2016) in "Schizophrenia risk from complex variation of complement component 4" applies this to psychiatric disease, while Magro et al. (2020) in "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases" shows acute pathological activation. Therapeutic guidelines in Padmanabhan et al. (2019) and Rovin et al. (2021) build on these insights.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Focus on complement therapeutics in glomerular and apheresis guidelines from Rovin et al. (2021) and Padmanabhan et al. (2019), alongside COVID-19 pathology in Magro et al. (2020), to explore clinical translation amid absent recent preprints.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Complement Factor H Polymorphism in Age-Related Macular Degene... | 2005 | Science | 4.5K | ✓ |
| 2 | A novel MHC class I–like gene is mutated in patients with here... | 1996 | Nature Genetics | 3.7K | ✕ |
| 3 | Complement: a key system for immune surveillance and homeostasis | 2010 | Nature Immunology | 3.5K | ✕ |
| 4 | A Novel Serum Protein Similar to C1q, Produced Exclusively in ... | 1995 | Journal of Biological ... | 3.2K | ✓ |
| 5 | Complement | 2001 | New England Journal of... | 2.9K | ✕ |
| 6 | Complement Factor H Polymorphism and Age-Related Macular Degen... | 2005 | Science | 2.4K | ✕ |
| 7 | Schizophrenia risk from complex variation of complement compon... | 2016 | Nature | 2.4K | ✓ |
| 8 | Complement associated microvascular injury and thrombosis in t... | 2020 | Translational research | 2.2K | ✓ |
| 9 | Guidelines on the Use of Therapeutic Apheresis in Clinical Pra... | 2019 | Journal of Clinical Ap... | 2.2K | ✕ |
| 10 | KDIGO 2021 Clinical Practice Guideline for the Management of G... | 2021 | Kidney International | 2.2K | ✓ |
Frequently Asked Questions
What role does complement factor H play in age-related macular degeneration?
A common variant in the complement factor H gene is associated with increased risk of age-related macular degeneration, as identified in a genome-wide screen of 96 cases and 50 controls. Klein et al. (2005) in "Complement Factor H Polymorphism in Age-Related Macular Degeneration" reported this intronic polymorphism among 116,204 single-nucleotide polymorphisms genotyped. Edwards et al. (2005) confirmed the association in "Complement Factor H Polymorphism and Age-Related Macular Degeneration".
How is the complement system involved in severe COVID-19?
Complement activation leads to microvascular injury and thrombosis in severe COVID-19 cases. Magro et al. (2020) detailed this in five patients in "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases". The findings underscore complement's contribution to endothelial damage in infection.
What are therapeutic interventions for complement-related disorders?
Eculizumab, a complement inhibitor, manages conditions like thrombotic microangiopathies and hemolytic uremic syndrome. Therapeutic apheresis is recommended for complement-driven diseases per Padmanabhan et al. (2019) in "Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue". KDIGO guidelines by Rovin et al. (2021) endorse such therapies for glomerular diseases.
How does complement factor H relate to other diseases?
Beyond AMD, complement dysregulation appears in schizophrenia via complex variation of complement component 4, as shown by Sekar et al. (2016) in "Schizophrenia risk from complex variation of complement component 4". Ricklin et al. (2010) describe complement's broader role in immune homeostasis in "Complement: a key system for immune surveillance and homeostasis".
What is the basic function of the complement system?
The complement system defends against pyogenic bacterial infection, bridges innate and adaptive immunity, and disposes of immune complexes. Walport (2001) outlines these activities in "Complement". It operates as part of innate immunity with antibody-mediated effector mechanisms.
Open Research Questions
- ? How do specific complement factor H polymorphisms quantitatively contribute to AMD progression beyond association?
- ? What mechanisms link complement component 4 variation to schizophrenia risk in neural tissues?
- ? Can targeted complement inhibition like Eculizumab prevent thrombosis in complement-driven COVID-19 microvascular injury?
- ? How does complement regulation differ in thrombotic microangiopathies versus glomerular diseases?
- ? What genetic interactions modulate complement activation in inflammatory diseases?
Recent Trends
No recent preprints or news coverage in the last 12 months indicates steady maturation rather than rapid shifts, with high-citation works like Magro et al. on COVID-19 complement pathology (2225 citations) and guidelines from Rovin et al. (2021) and Padmanabhan et al. (2019) (both 2175 citations) emphasizing evidence-based therapies across 50,054 total works.
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