Complement disorders and hereditary angioedema.

Area of Science:

• Immunology
• Biochemistry

Background:

• The complement system is a vital part of innate immunity, involving plasma factors for host defense and microbial destruction.
• Three distinct activation pathways exist: classical, alternative, and lectin, with two preceding adaptive immunity and not requiring antibodies.
• All pathways converge to activate C3, a key opsonic protein, leading to cell lysis and generation of factors like C5a.

Purpose of the Study:

• To review the complement system's activation pathways and their evolutionary significance.
• To highlight the prevalence and clinical implications of complement system defects, particularly regulatory protein defects.
• To discuss hereditary angioedema as a model for complement dysregulation.

Main Methods:

• Review of existing literature on complement pathways and deficiencies.
• Analysis of the evolutionary timeline of complement activation.
• Case discussion of CI inhibitor deficiency and hereditary angioedema.

Main Results:

• Complete deficiencies of complement proteins are rare; partial deficiencies of mannose-binding lectin are more common.
• Defects in complement regulatory proteins are more frequent than genetic deficiencies and can lead to uncontrolled inflammation.
• CI inhibitor deficiency is a significant defect associated with hereditary angioedema, with new treatments emerging.

Conclusions:

• The complement system's complexity extends beyond deficiencies to include crucial regulatory mechanisms.
• Dysregulation of the complement cascade, especially involving regulatory proteins, has significant clinical consequences.
• Understanding complement defects, like CI inhibitor deficiency, is essential for developing effective therapeutic strategies.