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Factor B activation products in patients with systemic lupus erythematosus. A marker of severe disease activity
L D Kerr1, B R Adelsberg, P Schulman
1Department of Medicine, Mount Sinai Medical Center, New York, New York.
Insights
Alternative complement pathway activation in systemic lupus erythematosus (SLE) patients indicates severe disease. This pathway may contribute to the development of severe SLE, impacting patient morbidity and mortality.
Area of Science:
- Immunology
- Rheumatology
- Complement System Biology
Background:
- Systemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis.
- The complement system, a crucial part of innate immunity, plays a role in SLE.
- Understanding complement activation patterns may offer insights into SLE severity and outcomes.
Purpose of the Study:
- To correlate complement activation patterns with clinical outcomes in SLE patients over two years.
- To investigate the role of classical and alternative complement pathways in SLE.
- To identify potential biomarkers for severe SLE.
Main Methods:
- Analyzed complement activation markers (C4a desArg, C4, Factor B, C3d, C3) in 51 SLE patients.
- Monitored classical pathway activation via C4 levels and alternative pathway via Factor B.
- Stratified patients into three groups based on complement activation patterns (C4, C3, Factor B).
Main Results:
- A significant difference in morbidity and mortality rates was observed in patients with C4, C3, and Factor B activation compared to others.
- The presence of the Ba fragment was significantly associated with cutaneous vasculitis.
- The Bb activation fragment was notably absent in activated plasma samples from SLE patients.
Conclusions:
- Activation of the alternative complement pathway may serve as a marker for severe SLE.
- The Bb fragment's absence and Ba's presence suggest specific roles in SLE pathogenesis.
- These findings highlight the alternative pathway's potential contribution to severe SLE pathology.
Abstract:
Complement activation patterns were determined in a group of 51 patients with systemic lupus erythematosus (SLE), and the clinical outcomes of these patients at 2 years were correlated with the complement activation patterns. Activation of the classical pathway was monitored by analysis of C4a desArg levels and total C4 levels, and activation of the alternative pathway was monitored by isoelectric focusing/immunofixation and quantitative analyses of Factor B. Activation of C3 (a general measure of complement activation) was determined by an enzyme-linked immunosorbent assay for C3d and by quantitative analysis of C3. Patients were stratified into 3 groups: those with C4 but not C3 activation; those with C4 and C3 but not Factor B activation; and those with C4, C3, and Factor B activation. At the end of 2 years, there was a statistically significant difference in the morbidity and mortality rates of the third group of SLE patients compared with those in the other 2 groups. There was also a statistically significant association between the presence of Ba and cutaneous vasculitis. Unlike the patterns seen with in vitro-activated serum or with membrane-activated plasma, the Bb activation fragment was not present in the activated plasma samples from the SLE patients. These data suggest that activation of the alternative complement pathway may be a marker for severe SLE and that the Bb fragment may be playing a role in the development of this more serious pathologic condition.