Complement component 3 deficiency

Complement component 3 (C3) deficiency is a rare primary immunodeficiency disorder caused by a complete or near-complete absence of complement component 3, a central protein in the complement system. C3 plays a pivotal role in all three complement activation pathways (classical, alternative, and lectin) and is essential for opsonization of pathogens, immune complex clearance, and inflammatory responses. The condition is also known as C3 deficiency or selective complement C3 deficiency. It is caused by pathogenic variants in the C3 gene located on chromosome 19p13.3. Patients with C3 deficiency typically present in early childhood with recurrent, severe bacterial infections, particularly caused by encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Common infections include pneumonia, meningitis, and sepsis. A significant proportion of affected individuals also develop immune complex-mediated glomerulonephritis, specifically membranoproliferative glomerulonephritis, which can progress to renal failure. This renal involvement results from impaired clearance of immune complexes due to the absence of functional C3. Some patients may also develop autoimmune manifestations, including features resembling systemic lupus erythematosus. There is no specific curative treatment for C3 deficiency. Management focuses on prompt and aggressive treatment of infections with appropriate antibiotics, prophylactic antibiotic therapy in some cases, and vaccination against encapsulated organisms, although vaccine efficacy may be reduced due to the complement deficiency. Fresh frozen plasma infusions have been used in some patients to temporarily restore C3 levels, but this approach carries risks including allergic reactions and is not a long-term solution. Renal disease is managed with standard nephrology care, and some patients may ultimately require renal transplantation. Genetic counseling is recommended for affected families.

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