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Complement components, C1 activation and disease activity in SLE
Insights
Systemic lupus erythematosus (SLE) involves complement system activation, particularly the classical pathway, indicated by decreased C1q, C4, and C3 levels during active disease. Complement activation is independent of disease activity.
Area of Science:
- Immunology
- Rheumatology
- Clinical Chemistry
Background:
- Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition and inflammation.
- The complement system plays a crucial role in SLE pathogenesis, but its precise activation pathways and markers require further elucidation.
Purpose of the Study:
- To investigate laboratory parameters, focusing on complement system activation, in SLE patients during active and inactive disease states.
- To correlate complement component levels with disease activity and renal manifestations.
Main Methods:
- Analysis of serum samples from 8 SLE patients during high and low disease activity periods.
- Measurement of complement components (C1q, C4, C3, C2, C1r-C1s-C1 inactivator complexes, factor B, I, H, D), C-reactive protein, and immune complexes.
- Utilized both immunochemical and functional assays for complement components.
Main Results:
- Elevated C1r-C1s-C1 inactivator complexes (C1r-C1s-Cl IA) indicated C1 activation, independent of disease activity.
- During active SLE, decreased levels of C1q, C4, C3, and functional C2 suggested classical pathway activation.
- Correlations were observed between C1r-C1s-Cl IA and C1q binding immune complexes in solid-phase assays.
Conclusions:
- The classical complement pathway is sequentially activated in active SLE.
- Complement activation, evidenced by C1r-C1s-Cl IA, occurs independently of disease flares.
- Further research is needed to understand the role of specific complement factors in SLE, particularly in cases with renal involvement.
Abstract:
Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.