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A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus
1John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Insights
Changes in C3 and C4 complement levels were not consistently linked to systemic lupus erythematosus (SLE) flares. However, decreasing complement levels correlated with increased renal and hematologic activity in SLE patients.
Area of Science:
- Immunology
- Rheumatology
- Clinical Chemistry
Background:
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune system dysregulation.
- Complement system proteins, such as C3 and C4, play a crucial role in immune responses and are often implicated in SLE pathogenesis.
- Understanding the relationship between complement levels and disease activity is vital for monitoring and managing SLE.
Purpose of the Study:
- To investigate the temporal relationship between changes in C3 and C4 complement levels and systemic lupus erythematosus (SLE) activity.
- To assess whether alterations in C3 and C4 precede or coincide with SLE flares as measured by five distinct global activity indices.
- To evaluate the association between C3 and C4 level changes and SLE activity within specific organ systems.
Main Methods:
- A longitudinal study involving 53 lupus patients observed monthly for one year.
- Systemic lupus erythematosus (SLE) disease activity and complement levels (C3, C4) were measured at each visit.
- Flare definitions included specific increases in physician's global assessment (PGA), M-SLEDAI, M-LAI, SLAM, and M-BILAG; logistic regression analyzed associations, controlling for prednisone dosage.
Main Results:
- Decreases in C3 and C4 levels were associated with concurrent increases in renal disease activity.
- Concurrent decreases in C3 were linked to reduced hematocrit, platelet, and white blood cell counts.
- Concurrent decreases in C4 were associated with reduced hematocrit and platelet counts.
- While not consistently linked to global SLE flares, specific complement changes correlated with organ-specific activity.
Conclusions:
- Decreases in complement levels (C3, C4) are not consistently predictive of overall systemic lupus erythematosus (SLE) flares based on global activity measures.
- However, declining C3 and C4 levels are significantly associated with concurrent increases in renal and hematologic manifestations of SLE.
- These findings suggest that complement levels may serve as valuable indicators for specific organ system involvement in SLE patients.
Objective:
To determine the degree to which changes in C3 and C4 precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 global activity indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG), and to evaluate the association between changes in C3 and C4 levels and SLE activity in individual organ systems.
Methods:
Fifty-three lupus patients were observed monthly for 1 year in a longitudinal study. Lupus disease activity and complement levels were measured at each visit. Lupus flare was defined as a 1.0 (or greater) increase in the PGA, a 3-point increase in the M-SLEDAI, a 0.1 increase in the M-LAI, a 3-point increase in the SLAM, or a 4-point increase in the M-BILAG within a 1-month period. Flare rates were calculated for subgroups defined by previous (1 month before) or concurrent changes in complement levels. Logistic regression models were used to determine the significance of the association between recent changes in complement levels and flare, controlling for prednisone dosage. Similar models were used to assess the association between changes in C3 or C4 levels and increased SLE activity in specific organ systems.
Results:
Lupus flares occurred at 12% of visits based on the PGA, 19% based on the M-SLEDAI, 25% based on the M-LAI, 13% based on the SLAM, and 12% based on the M-BILAG. Recent changes in C3 and C4 levels were not associated with flares based on 3 of the 5 activity indices. Flares defined by the M-LAI were more frequent when there was a concurrent decrease in C3 (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.1-3.1) or C4 (OR 2.1, 95% CI 1.3-3.6). Higher flare rates, as defined by the SLAM, were associated with previous increases in C3 (OR 1.6, 95% CI 1.0-2.6) and C4 (OR 2.2, 95% CI 1.2-3.9). When individual organ systems were analyzed, decreases in C3 and C4 were associated with a concurrent increase in renal disease activity (OR 2.2, 95% CI 1.4-3.5 and OR 1.9, 95% CI 1.1-3.4, respectively). Decreases in C3 were also associated with concurrent decreases in the hematocrit (OR 4.6, 95% CI 1.7-12.3), platelet (OR 2.5, 95% CI 1.5-4.1), and white blood cell (OR 2.2, 95% CI 1.3-3.6) counts. Previous increases in C3 levels were associated with a decrease in platelets (OR 1.7, 95% CI 1.1-2.7). A decrease in C4 was associated with a concurrent decrease in the hematocrit level (OR 3.2, 95% CI 1.3-7.5) and platelet count (OR 1.6, 95% CI 1.0-2.5).
Conclusion:
Decreases in complement levels were not consistently associated with SLE flares, as defined by global measures of disease activity. However, decreasing complement was associated with a concurrent increase in renal and hematologic SLE activity.