From the Guidelines
Elevated C3 complement levels should be managed by identifying and treating the underlying cause of inflammation, rather than treating the elevated C3 itself. This approach is supported by recent guidelines, such as the 2021 KDIGO clinical practice guideline for the management of glomerular diseases, as commented on by 1. The underlying cause of elevated C3 can be an infectious or autoimmune disease, and thus screening for these conditions is essential. In some cases, malignancy should also be considered as a source of chronic antigenemia.
Some key points to consider in the management of elevated C3 complement include:
- Identifying the underlying cause of inflammation, which can include infections, autoimmune diseases, or malignancies
- Screening for underlying infections, such as HBV or HCV, bacterial or parasitic disease, or autoimmune disease with appropriate serologies, as recommended by 1
- Considering a search for a paraprotein, as monoclonal proteins can affect the complement cascade, and performing serum and urine immunoelectrophoresis and immunofixation, as well as a serum free light chain analysis, as suggested by 1
- Monitoring C3 levels over time to assess the effectiveness of treatment for the underlying condition
In terms of treatment, focusing on the underlying cause of inflammation is crucial, and specific treatments may vary depending on the underlying condition. For example, in patients with C3 glomerulopathy (C3G) and moderate-to-severe disease, treatment with MMF plus glucocorticoids may be considered, and if this fails, eculizumab may be an option, as recommended by 1. However, the primary goal should always be to address the underlying cause of inflammation, rather than simply treating the elevated C3 levels.
From the Research
Elevated C3 Complement
- Elevated serum complement C3 levels have been associated with various conditions, including prehypertension 2 and C3 glomerulopathy 3.
- In C3 glomerulopathy, uncontrolled complement C3 activation via the alternative pathway results in glomerular C3 deposition and, in many cases, progressive renal failure 3.
- The presence of the C3F allele has generally been linked with a detrimental outcome, suggesting that C3 polymorphism may have biological and clinical consequences 4.
- Elevated C3 levels have been found to be associated with prehypertension in an adult population, suggesting that pro-inflammatory immune response may be involved in the prehypertensive state 2.
Related Conditions and Treatments
- Mycophenolate mofetil has been used to treat C3 glomerulopathy, with some patients achieving durable remission 3.
- Azathioprine and mycophenolate mofetil have been compared as treatments for myasthenia gravis, with no significant difference in clinical outcomes found between the two drugs 5.
- Immunomodulatory treatments, including azathioprine, interferon beta-1a, and methotrexate, have been studied as potential treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but low-quality evidence does not show significant benefit from these treatments 6.