From the Guidelines
Elevated complement C3 levels should prompt an evaluation for underlying infections, autoimmune diseases, or malignancy, with treatment focusing on the underlying cause, as recommended by the most recent guidelines 1. When complement C3 is elevated, it typically indicates an active inflammatory response, which could be due to various conditions such as infections, autoimmune diseases, or certain types of cancer. The complement system, including C3, plays a crucial role in the immune response, helping to clear pathogens and damaged cells from the body.
Key Considerations
- Elevated C3 levels are not a disease in themselves but rather a marker of immune system activation.
- Common causes of elevated C3 include acute and chronic infections, autoimmune conditions like rheumatoid arthritis, certain cancers, and metabolic disorders.
- The presence of a monoclonal protein should be considered, especially in adult patients with complement-dominant membranoproliferative glomerulonephritis (MPGN) or those diagnosed with C3 glomerulonephritis (C3G) at an age of 50 years or older, as suggested by 1.
- Evaluation should include screening for underlying infections (e.g., HBV, HCV, bacterial, or parasitic diseases) and autoimmune diseases with appropriate serologies, as well as consideration of malignancy as a source of chronic antigenemia 1.
Diagnostic Approach
- A comprehensive diagnostic approach is necessary, including complete blood count, other inflammatory markers (CRP or ESR), and specific tests based on the patient's symptoms.
- Serum and urine immunoelectrophoresis, immunofixation, and serum free light chain analysis are recommended for adult patients with C3GN to identify any paraprotein that might be affecting the complement cascade 1.
- The goal of treatment should be to address the underlying cause of the elevated C3, rather than the elevation itself, to improve patient outcomes in terms of morbidity, mortality, and quality of life.
From the Research
Elevated Complement C3
- Elevated serum complement C3 levels have been associated with various conditions, including prehypertension 2 and autoimmune diseases 3, 4.
- Complement C3 is a central hub of the complement-related immune system, and its activation plays a crucial role in inflammation, autoimmune disorders, and vision loss 5.
- Studies have shown that elevated C3 levels are associated with an increased risk of prehypertension in adults 2, and may also be involved in the pathogenesis of autoimmune hemolytic anemia 4.
- The measurement of C3 levels can be used as a diagnostic tool to evaluate complement activation and disease activity in various conditions, including autoimmune diseases 3 and age-related macular degeneration 5.
- Polymorphisms in the C3 gene have been linked to disease states, with the C3F allele generally associated with a detrimental outcome 6.
Clinical Significance
- Elevated C3 levels may be a useful biomarker for the diagnosis and monitoring of diseases associated with complement activation, such as autoimmune hemolytic anemia and prehypertension.
- The association between C3 levels and disease activity suggests that reducing inflammation may be a potential therapeutic strategy for these conditions 2.
- Further studies are needed to fully understand the biological and clinical consequences of C3 polymorphism and its role in disease pathogenesis 6.