Reference ranges for serum C4 concentrations in subjects with and without C4 null alleles

Area of Science:

• Immunogenetics
• Clinical Chemistry
• Complement System Biology

Background:

• The complement system, particularly the C4 component, plays a vital role in immune responses.
• Variations in C4 gene expression, such as C4 null alleles, can influence serum C4 concentrations.
• Understanding these variations is important for interpreting clinical laboratory results.

Purpose of the Study:

• To investigate the relationship between C4 null alleles and serum C4 concentrations.
• To establish reference ranges for serum C4 levels based on the number of C4 null alleles.
• To assess the impact of C4 null alleles on C4 concentrations in healthy subjects and those with type I diabetes mellitus.

Main Methods:

• Serum C4 concentrations were measured in a cohort of healthy individuals and patients with type I diabetes mellitus.
• C4 allotyping was performed to determine the presence and number of C4 null alleles in subjects.
• Statistical analysis was used to compare C4 concentrations across different C4 null allele groups.

Main Results:

• A wide range of serum C4 concentrations was observed overall.
• Subjects with two C4 null alleles exhibited significantly lower C4 concentrations compared to those with no null alleles (mean 0.2 vs. 0.37 g/l, p < 0.001).
• Individuals with one C4 null allele showed intermediate C4 concentrations, also significantly lower than those without null alleles (mean 0.24 vs. 0.37 g/l, p < 0.001).

Conclusions:

• The number of C4 null alleles present directly impacts serum C4 concentrations.
• Defined reference ranges for serum C4 are established based on C4 null allele status.
• Clinical interpretation of low serum C4 levels must consider the individual's C4 null allele genotype.