Hereditary C6 deficiency in man

Area of Science:

• Immunology
• Genetics
• Complement System

Background:

• The complement system is crucial for innate and adaptive immunity.
• Complement component 6 (C6) is essential for the formation of the membrane attack complex (MAC).
• Deficiencies in complement components can lead to increased susceptibility to infections and autoimmune diseases.

Purpose of the Study:

• To characterize a novel case of complement component 6 (C6) deficiency in a human.
• To investigate the inheritance pattern and functional consequences of C6 deficiency in a human kindred.
• To compare C6 deficiency in humans with previously studied animal models.

Main Methods:

• Serum CH50 titrations and functional assays for all complement components.
• Detection of C6 deficiency using functional assays and antigenic analysis with monospecific anti-C6 antibody.
• Assessment of bactericidal activity, neutrophil chemotaxis, immune adherence, and PNH red cell lysis.
• Genetic analysis of the affected kindred to determine inheritance patterns.

Main Results:

• A 18-year-old female presented with undetectable C6 levels in serum and plasma.
• Hemolytic activity was restored upon addition of purified C6.
• Parents and 5 out of 6 siblings exhibited approximately half-normal C6 levels, indicating autosomal inheritance.
• The C6-deficient individual showed absent bactericidal activity and PNH red cell lysis but normal chemotaxis and coagulation functions.

Conclusions:

• This study documents the first human kindred with complement component 6 (C6) deficiency.
• C6 deficiency in humans follows a classic Mendelian autosomal inheritance pattern.
• Unlike C6-deficient rabbits, homozygous C6 deficiency in humans does not affect chemotactic or coagulation functions.