ArticleThe Journal of clinical investigation2011
Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Host genetic variability and pneumococcal disease: a systematic review and meta-analysis.BMC medical genomics · 2019Pooled it
- Stem cell-derived brain-like endothelial cells to interrogateVirulence · 2025Article
- Pharmacologic depletion of border-associated macrophages worsens disease in a mouse model of meningitis.Acta neuropathologica communications · 2025Article
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- Innate Immune Mechanisms in the Central Nervous System.Advances in experimental medicine and biology · 2025Review
- Cerebrovascular Complications in Bacterial Meningitis.Stroke (Hoboken, N.J.) · 2025Review
- Review
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Combining antibiotic with anti-TLR2/TLR13 therapy prevents brain pathology in pneumococcal meningitis.JCI insight · 2024Article
- Blockade of C5a receptor unleashes tumor-associated macrophage antitumor response and enhances CXCL9-dependent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models.Brain communications · 2024Review
- Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood-brain barrier function.Journal of neuroinflammation · 2023Article
- The Relationship between Complement ComponentsGenes · 2023Article
- Low serum complement level is associated with higher mortality in tuberculous meningitis: a retrospective cohort study.Encephalitis (Seoul, Korea) · 2023Article
- The role of plasminogen activator inhibitor-2 in pneumococcal meningitis.Acta neuropathologica communications · 2022Article
- Review
- The Influence of an Elastase-Sensitive Complement C5 Variant on Lupus Nephritis and Its Flare.Kidney international reports · 2021Article
- Interaction Between the Complement System and Infectious Agents - A Potential Mechanistic Link to Neurodegeneration and Dementia.Frontiers in cellular neuroscience · 2021Review
- Investigation of Association of Complement 5 Genetic Polymorphisms with Sepsis and Sepsis-Induced Inflammatory Responses.Journal of inflammation research · 2021Article
- Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κβ and ASK1 Pathways.Journal of molecular neuroscience : MN · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.
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Registered trials
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.