Common polymorphisms in the complement system and susceptiblity to bacterial meningitis
Kirsten S Adriani1, Matthijs C Brouwer, Madelijn Geldhoff
1Department of Neurology, Center of Infection and Immunity Amsterdam-CINIMA, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100DD Amsterdam, The Netherlands.
The Journal of Infection
|October 17, 2012
Summary
Genetic variations in complement component 3 (C3) influence susceptibility to bacterial meningitis. A specific C3 single nucleotide polymorphism (SNP) was linked to reduced risk, highlighting the complement system
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Inter-individual differences in susceptibility to bacterial meningitis are not fully understood.
- The complement system plays a crucial role in innate immunity against bacterial pathogens.
Purpose of the Study:
- To investigate the association between genetic variations in the complement system and susceptibility to community-acquired bacterial meningitis.
- To explore the functional consequences of identified genetic variations on complement activation.
Main Methods:
- A prospective nationwide genetic association study was conducted.
- 17 common single nucleotide polymorphisms (SNPs) in complement genes were genotyped in patients with bacterial meningitis and controls.
- Complement levels in cerebrospinal fluid (CSF) were measured to assess functional consequences.
Main Results:
- A significant association was found between a specific SNP in complement component 3 (C3), rs1047286 (Pro314Leu), and reduced susceptibility to bacterial meningitis.
- The protective Leu/Leu genotype of rs1047286 was less frequent in patients compared to controls (1% vs. 5%).
- This SNP is in linkage disequilibrium with rs2230199 (C3 Arg102Gly), which was associated with altered C3, C5a, and terminal complement complex (TCC) levels in CSF, indicating reduced complement system activation.
Conclusions:
- A common single nucleotide polymorphism in C3 is associated with susceptibility to community-acquired bacterial meningitis.
- Genetic variations in C3 may influence an individual's risk of developing bacterial meningitis by affecting complement system function.
More Related Videos
Related Concept Videos
01:27Complement System
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
01:26Bacterial Meningitis II: Pathophysiology
Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
01:22Bacterial Meningitis I: Introduction
Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...
01:23Antimicrobial Proteins
Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
01:31Defense Against Bacterial Pathogens
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:26Factors Affecting the Risk of Infection
The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin create...
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin create...