From the Guidelines
Complement levels are low in lupus due to the consumption of complement proteins during the inflammatory process, which is supported by the presence of anti-C1q antibodies in patients with active lupus nephritis 1. The immune system in lupus patients becomes overactive, producing autoantibodies that form immune complexes with self-antigens, activating the complement system and leading to the consumption of complement proteins like C3 and C4.
- The prevalence of anti-C1q antibodies in patients with SLE varies between 30% and 60%, and they are found in almost 100% of patients with active lupus nephritis 1.
- These antibodies are associated with SLE flare-ups and have been suggested as disease-activity biomarkers 1.
- The critical negative predictive value of these antibodies must be emphasized, i.e., patients with lupus nephritis are doubtful to experience a flare-up in the absence of anti-C1q 1. The degree of complement depletion often correlates with disease activity, making complement levels (particularly C3 and C4) useful laboratory markers for monitoring lupus activity and response to treatment, as recommended by expert panels 1.
- It is recommended to always use anti-dsDNA and complement levels in patient follow-up, even if they were negative/normal in previous monitoring visits 1. Low complement levels, especially when accompanied by rising anti-dsDNA antibody titers, may indicate an impending disease flare, allowing clinicians to adjust treatment before symptoms worsen.
From the Research
Complement Levels in Lupus
- Complement levels are often low in patients with systemic lupus erythematosus (SLE) due to the consumption of complement components during the disease process 2, 3, 4, 5, 6.
- The low complement levels are associated with disease activity and damage in SLE patients 2, 3, 4.
- Complement activation is a key event in the pathogenesis of tissue inflammation and injury in SLE, and elevated levels of complement split products are found in SLE patients 3, 4, 5.
Mechanisms of Low Complement Levels
- The consumption of complement components, such as C3 and C4, is increased in SLE patients due to the formation of immune complexes and the activation of the complement system 5, 6.
- The presence of antiphospholipid antibodies (aPL) is associated with low levels of complement C3 and C4 in SLE patients, suggesting a higher consumption of these components in aPL-positive patients 6.
- Genetic defects in complement components, such as C1q, C1s, C1r, C2, or C4, can also contribute to the development of SLE and low complement levels 4.
Clinical Implications
- Low complement levels are associated with an increased risk of organ involvement, such as lupus glomerulonephritis, and haematological involvement in SLE patients 2, 3.
- The measurement of complement levels and split products can be useful in diagnosing and monitoring SLE, as well as predicting disease activity and damage 3, 4, 5.