A novel mutation in the complement component 3 gene in a patient with selective IgA deficiency

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Recurrent infections, particularly those caused by Streptococcus pneumoniae, can indicate underlying primary immunodeficiencies (PIDs).
• Complement component 3 (C3) plays a critical role in both innate and adaptive immunity, and its deficiency can lead to increased susceptibility to infections.

Observation:

• A 16-year-old male with consanguineous parents presented with recurrent pneumonia and bronchiectasis due to S. pneumoniae.
• The patient exhibited severely reduced C3 and immunoglobulin A (IgA) levels.
• Genetic analysis identified a novel homozygous missense mutation (c.C4554G, p.Cys1518Trp) in the C3 gene, affecting a conserved amino acid and disulfide bond.

Findings:

• The identified C3 mutation disrupted a disulfide bond in the C345C domain, leading to severely reduced C3 levels in the patient and moderate reduction in carrier parents.
• The patient also had selective IgA deficiency.
• Post-vaccination with an unconjugated polysaccharide vaccine against S. pneumoniae, the patient showed significant clinical improvement.

Implications:

• This study reports a novel C3 gene mutation associated with recurrent S. pneumoniae infections and selective IgA deficiency.
• The findings underscore the therapeutic importance of S. pneumoniae vaccination in managing primary immunodeficiency disorders, especially in patients susceptible to this pathogen.
• This highlights the critical role of C3 in immune function and the potential for targeted therapies in PID management.