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Hereditary human complement C3 deficiency owing to reduced levels of C3 mRNA
A G Ulbrich1, M P Florido, V Nudelman
1Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
Abstract:
An 8-year-old son (L.A.S.) of consanguineous parents, presented recurrent bacterial infections, vasculitis and extremely low levels of serum C3 (0.15 microg/ml). The classical and alternative pathway haemolytic activities and the generation of opsonins and chemotactic factors derived from the activation of the complement system were markedly affected in the proband's serum. An in vitro addition of purified C3 restored the classical pathway-dependent haemolytic activity of his serum. Autoradiographs of the proband's lipopolysaccharide (LPS)-stimulated and 35S-labelled fibroblast supernatants after that the SDS-PAGE revealed no C3 alpha or beta chains. The amount of C3 mRNA synthesized by the proband's fibroblasts, as evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assays, was greatly reduced.
Insights
A child with recurrent infections had severely low complement component 3 (C3) levels, indicating a critical role for C3 in immune defense. Genetic analysis revealed significantly reduced C3 messenger RNA (mRNA) in his cells.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Recurrent bacterial infections and vasculitis can indicate underlying primary immunodeficiencies.
- The complement system, particularly complement component 3 (C3), is crucial for innate and adaptive immunity.
Observation:
- An 8-year-old presented with recurrent infections and vasculitis, exhibiting extremely low serum C3 levels.
- The patient's serum showed impaired classical and alternative complement pathway hemolytic activities.
Findings:
- In vitro addition of purified C3 restored the classical pathway hemolytic activity, suggesting C3 deficiency.
- Analysis of fibroblast supernatants revealed an absence of C3 alpha and beta chains.
- Reverse transcription-polymerase chain reaction (RT-PCR) assays demonstrated significantly reduced C3 mRNA synthesis in the patient's fibroblasts.
Implications:
- This case highlights a severe genetic defect in C3 production, leading to immunodeficiency.
- Understanding C3 deficiency is vital for diagnosing and managing patients with recurrent infections and complement abnormalities.
- Further research into complement component deficiencies can elucidate their role in various autoimmune and infectious diseases.