Inherited deficiencies of complement components in man

Area of Science:

• Immunology
• Genetics
• Complement System

Background:

• Isolated inherited deficiencies of complement proteins are recognized, mostly as autosomal recessive traits.
• Deficiencies in early components (C1, C4, C2) elevate the risk of immune complex diseases like lupus.
• Deficiencies in later components (C3, factor I, factor H, properdin, C5-C8) lead to increased susceptibility to specific bacterial or neisserial infections.

Purpose of the Study:

• To review the clinical manifestations and genetic basis of inherited complement protein deficiencies.
• To highlight the association between specific complement deficiencies and distinct disease risks.
• To discuss the pathophysiology and management of hereditary angioedema due to C1 inhibitor deficiency.

Main Methods:

• Review of existing literature on complement deficiencies and associated clinical outcomes.
• Analysis of inheritance patterns (autosomal recessive, autosomal dominant) for various deficiencies.
• Examination of the role of C1 inhibitor deficiency in hereditary angioedema and potential treatments.

Main Results:

• Complement deficiencies are linked to specific health risks: immune complex disease, pyogenic bacterial infections, or neisserial infections.
• C1 inhibitor deficiency, an autosomal dominant trait, causes angioedema and C4/C2 consumption.
• A plasmin-modified C2 fragment is implicated in angioedema; androgens may help manage symptoms.

Conclusions:

• Inherited complement deficiencies represent a spectrum of immune dysregulation with varied clinical consequences.
• Understanding these deficiencies is crucial for diagnosis, risk assessment, and targeted management.
• Hereditary angioedema management may involve addressing biochemical abnormalities and preventing attacks, with androgens showing therapeutic potential.