From the Guidelines
In patients with Systemic Lupus Erythematosus (SLE), C4 levels are typically decreased, often falling below the normal range of 10-40 mg/dL, as supported by the most recent evidence 1. During active disease flares, C4 levels may drop significantly, sometimes to values less than 10 mg/dL. This reduction occurs because C4 is consumed during the inflammatory process characteristic of SLE. The complement system becomes activated when immune complexes form between autoantibodies and self-antigens, leading to C4 depletion as it participates in the classical complement pathway. Some key points to consider in SLE management include:
- Monitoring C4 levels is clinically valuable, as persistently low levels often correlate with disease activity, particularly in patients with lupus nephritis 1.
- Serial measurements of C4, rather than isolated values, provide more meaningful information about disease progression and response to treatment in SLE patients.
- The use of anti-dsDNA autoantibodies can also be helpful in monitoring disease activity, especially when used in conjunction with C4 levels 1.
- It is essential to note that some patients may have chronically low C4 levels even during disease remission due to genetic factors affecting complement production. The most recent study 1 provides the highest quality evidence for the management of SLE, and its recommendations should be prioritized in clinical practice.
From the Research
C4 Levels in SLE Patients
- C4 levels are often low in patients with Systemic Lupus Erythematosus (SLE), particularly during active disease or renal involvement 2, 3.
- A study found that 84.6% of patients with active renal involvement had low C4 levels, and 53% of non-renal flares also had low C4 levels 2.
- In patients with SLE in remission, C4 consumption (C4d/C4) was found to increase, which can lead to lower serum C4 concentrations 4.
- Another study found that C4 levels were lower in SLE patients with antiphospholipid antibodies (aPL) compared to those without aPL 3.
- The relationship between C4 and C3 levels in SLE patients is complex, with some studies suggesting that C3 levels are more sensitive and specific for SLE activity than C4 levels 5.
- Pediatric SLE patients can be categorized into three distinct groups based on their serum C4 protein profiles, with some patients having persistently low C4 levels and others experiencing periodic fluctuations in C4 levels 6.
Factors Influencing C4 Levels
- Disease activity and organ involvement can affect C4 levels in SLE patients 2, 3.
- C4 consumption and production can influence serum C4 concentrations in SLE patients 4.
- Genetic factors, such as C4 allotypic expression, may play a minimal role in determining C4 levels in SLE patients 4.
- Antiphospholipid antibodies (aPL) can be associated with lower C4 levels in SLE patients 3.