Common Genetic Variants in the Complement System and their Potential Link with Disease Susceptibility and Outcome of Invasive Bacterial Infection

Abstract

Streptococcus pneumoniae and Neisseria meningitidis are pathogens that frequently colonize the nasopharynx in an asymptomatic manner but are also a cause of invasive bacterial infections mainly in young children. The complement system plays a crucial role in humoral immunity, complementing the ability of antibodies to clear microbes, thereby protecting the host against bacterial infections, including S. pneumoniae and N. meningitidis. While it is widely accepted that complement deficiencies due to rare genetic variants increase the risk for invasive bacterial infection, not much is known about the common genetic variants in the complement system in relation to disease susceptibility. In this review, we provide an overview of the effects of common genetic variants on complement activation and on complement-mediated inflammation.

Keywords: Common genetic variants; Complement system; Disease susceptibility; Inflammation; Single nucleotide polymorphisms; Streptococcus pneumoniae.

Fig. 1

Some complement evasion proteins from Streptococcus pneumoniae and Neisseria meningitidis. Both S. pneumoniae and N. meningitidis use complement evasion mechanisms to circumvent opsonization (and killing) by the complement system. Both pathogens use similar mechanisms and different complement evasion mechanisms to counteract the complement system.

Fig. 2

Schematic representation of the 3 different activation pathways of the complement system. Depicted are the complement components that contain either a deficiency and/or an SNP that is discussed in this review.

Fig. 3

Effect of complement activity on risk for inflammatory disorders and risk for infections.

Fig. 4

Complement as a double-edged sword: effects of SNPs in complement ­factors on immunity.