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Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
María García-González1, Fuensanta Gómez-Bernal2, Juan C Quevedo-Abeledo3
1Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain.
Insights
Complement (C) pathways, including Classical (CL), Lectin (LE), and Alternative (AL), are linked to systemic lupus erythematosus (SLE) features. Disease damage correlates with higher C pathway function, while specific autoantibodies are associated with C activation.
Area of Science:
- Immunology
- Rheumatology
- Complement System Biology
Background:
- Comprehensive characterization of Classical (CL), Lectin (LE), and Alternative (AL) complement pathways in systemic lupus erythematosus (SLE) patients is lacking.
- Understanding complement system function is crucial for SLE pathogenesis and management.
Purpose of the Study:
- To assess the function of the three complement cascades (CL, LE, AL) in SLE patients using functional assays and protein measurements.
- To investigate the relationship between complement system activity and clinical characteristics in SLE.
Main Methods:
- Functional assays for CL, LE, and AL complement pathways were performed on 284 SLE patients.
- Linear regression analysis was used to correlate complement function with disease activity, severity, and damage.
Main Results:
- Lower functional test values were more frequent for AL and LE pathways compared to CL.
- Clinical activity was not associated with reduced complement pathway function.
- Increased DNA binding showed a negative correlation with most complement pathways, while disease damage correlated positively.
- Anti-ribosome, anti-nucleosome, and IgG anti-β2 glycoprotein antibodies demonstrated significant relationships with complement activation, particularly via LE, CL, and AL pathways, respectively.
Conclusions:
- All three complement pathways (CL, LE, AL) are implicated in SLE features and disease profiles.
- Accrued disease damage is associated with enhanced complement pathway function.
- Specific autoantibodies, including anti-DNA, anti-ribosomes, anti-nucleosomes, and antiphospholipid antibodies, are strongly linked to complement activation in SLE.
Background:
To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.
Methods:
New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.
Results:
Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.
Conclusion:
Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
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