From the Guidelines
Complement C3 and C4 levels can be used to assess treatment response in certain conditions, particularly in autoimmune diseases like systemic lupus erythematosus (SLE), where low levels often indicate active disease. Monitoring these complement proteins is valuable as their levels typically normalize with successful treatment, making them useful biomarkers for treatment effectiveness 1. For example, in lupus nephritis, physicians might check complement levels every 1-3 months during active treatment and less frequently during maintenance therapy. The utility of complement monitoring stems from their role in the immune system - these proteins are consumed during immune complex formation and inflammation, so their depletion suggests ongoing immune activation. However, complement levels should not be used in isolation but rather as part of a comprehensive assessment including clinical symptoms, other laboratory markers, and sometimes imaging or tissue studies. Interpretation requires understanding the patient's baseline levels, as some individuals naturally have lower complement values, and changes over time are often more informative than absolute values. Key points to consider include:
- Serum C3 has generally higher sensitivity than serum C4 for active lupus nephritis, but both tests have modest specificity 1.
- Changes in serological tests, including complement levels, are more important predictors of concurrent or impending disease flare than their absolute levels 1.
- These tests should be repeated no more than monthly, and in the absence of proteinuria, active serology and/or urine sediment is not an indication for pre-emptive treatment but dictates closer monitoring of patients 1. Given the most recent and highest quality evidence, the monitoring of complement C3 and C4 levels, as part of a comprehensive assessment, is recommended for assessing treatment response in SLE and lupus nephritis 1.
From the Research
Complement C3 and C4 Levels in Assessing Treatment Response
- Complement C3 and C4 levels can be used to assess disease activity in systemic lupus erythematosus (SLE) patients, as decreased serum complement levels are associated with disease flares 2, 3, 4, 5.
- However, it is essential to note that decreased serum complement is not consistently associated with disease flares, and other factors such as inflammation and immune-complex formation can influence complement levels 2, 6.
- Studies have shown that C3d, a complement split product, and the C3d/C3 ratio can provide sensitive markers for disease activity in SLE, reflecting complement activation better than C3, C4, and CH50 4.
- Serum complement proteins, including C3 and C4, can be used to distinguish between clinical subsets and organ damage in SLE, with C3 and C4 levels being lower in patients with active nephritis 3.
- Reference distributions for complement proteins C3 and C4 have been established, providing a practical and simple approach to interpreting measured blood levels of these components 6.
- Clinicians should consider the intensity of the inflammatory drive, the timing of the suspected clinical process, and the possible existence of benign circumstances when interpreting complement levels 6.
- Autoantibody testing and complement testing should be done in all suspected SLE cases to aid in early detection and reduce end-organ damage 5.