From the Guidelines
Elevated serum C3 levels are not typically a primary diagnostic concern and usually represent an acute phase reaction rather than a specific disease. The diagnostic approach involves first confirming the elevation with repeat testing and then investigating underlying causes such as acute inflammation, infections, or certain malignancies. No specific treatment targets elevated C3 itself; instead, management focuses on addressing the underlying condition causing the elevation. Common causes include acute bacterial infections, certain cancers, inflammatory conditions like rheumatoid arthritis, and obstructive biliary disease. Laboratory workup should include a complete blood count, inflammatory markers (ESR, CRP), liver function tests, and potentially imaging studies based on clinical suspicion, as suggested by recent guidelines 1. Unlike low C3 levels, which are more clinically significant and suggest complement consumption in conditions like lupus nephritis or membranoproliferative glomerulonephritis, elevated C3 is generally a reactive finding. The complement system is part of the innate immune response, and C3 is produced primarily by the liver as part of the acute phase response to inflammation. Once the underlying condition is successfully treated, C3 levels typically normalize without specific intervention. In cases where C3 glomerulonephritis (C3GN) is suspected, a comprehensive complement analysis is necessary to assist with the diagnosis, and screening for underlying infections or autoimmune diseases should be considered, as recommended in the commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1. Key points to consider in the diagnostic and treatment approach include:
- Confirming the elevation of serum C3 levels with repeat testing
- Investigating underlying causes such as acute inflammation, infections, or certain malignancies
- Focusing management on addressing the underlying condition causing the elevation
- Considering a comprehensive complement analysis and screening for underlying infections or autoimmune diseases in cases of suspected C3GN.
From the Research
Diagnostic Approach for Elevated Serum C3 Levels
Elevated serum C3 levels can be associated with various conditions, including:
- Atherosclerosis: High C3 levels have been linked to the progression of atherosclerosis, particularly in women 2.
- Pre-eclampsia: Serum C3 and C4 levels can help differentiate between systemic lupus erythematosus (SLE) activity and pre-eclampsia in pregnant women 3.
- IgA nephropathy: Fluctuations in serum C3 levels can reflect disease activity and metabolic background in patients with IgA nephropathy 4.
- Autoimmune hemolytic anemia: Reduced serum C3 levels have been observed in AIHA patients, particularly those with warm AIHA secondary to connective tissue diseases and cold agglutinin disease/cold agglutinin syndrome 5.
- Renal ANCA-associated vasculitis: Low serum C3 levels at diagnosis have been associated with poor prognosis in patients with renal ANCA-associated vasculitis 6.
Treatment Approach for Elevated Serum C3 Levels
The treatment approach for elevated serum C3 levels depends on the underlying condition. Some possible treatment strategies include:
- Managing atherosclerosis risk factors, such as hypertension and hyperlipidemia, to slow disease progression 2.
- Differentiating between SLE activity and pre-eclampsia in pregnant women to guide treatment decisions 3.
- Monitoring and managing IgA nephropathy disease activity and metabolic alterations to slow disease progression 4.
- Targeted treatment strategies for AIHA, such as immunosuppressive therapy or rituximab, based on serum complement levels and clinical characteristics 5.
- Immunosuppressive treatment for renal ANCA-associated vasculitis, with consideration of serum C3 levels as a prognostic factor 6.