Inherited complement deficiencies

Area of Science:

• Immunology
• Genetics

Background:

• Genetic deficiencies in complement system components are known for classical pathway, membrane attack complex, Factor I, Factor H, and properdin.
• Homozygous deficiencies for Factor B and Factor D of the alternative pathway remain uncharacterized.
• Complement deficiency studies offer direct insights into the in vivo role of the complement system.

Purpose of the Study:

• To review the known complement deficiency states and their clinical implications.
• To highlight the role of complement in resistance to bacterial infections, especially Neisseria.
• To explore the unexpected association between complement deficiencies and immune-complex diseases.

Main Methods:

• Review of existing literature on complement deficiencies.
• Analysis of in vitro and in vivo studies on complement function.
• Discussion of the pathogenesis of infections and immune-complex diseases in complement-deficient individuals.

Main Results:

• Complement deficiencies are strongly associated with increased susceptibility to bacterial infections, particularly Neisseria, due to impaired phagocytosis and inflammation.
• An unexpected link exists between complement deficiencies and immune-complex diseases, including systemic lupus erythematosus.
• The complement system is vital for immune complex solubilization and clearance, and its deficiency can lead to disease persistence.

Conclusions:

• The complement system plays a critical role in host defense against bacterial pathogens.
• Complement deficiencies contribute to the development of immune-complex diseases through impaired immune complex handling.
• Understanding complement deficiencies provides crucial insights into immune system function and disease pathogenesis.