Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus...

Area of Science:

• Immunology
• Nephrology
• Autoimmunity

Background:

• Autoantibodies against complement component C1q (anti-C1q) are established biomarkers in lupus nephritis (LN), linked to renal injury.
• The pathogenic role and frequency of autoantibodies against other C1 complex components, such as C1r, C1s, and C1 Inhibitor (C1-Inh), are less understood in LN.
• Understanding these autoantibodies can provide insights into LN pathogenesis and disease severity.

Purpose of the Study:

• To screen lupus nephritis patients for autoantibodies against C1q, C1r, C1s, and C1-Inh.
• To evaluate the association of these autoantibodies with disease activity, severity, and renal histology.
• To investigate the functional impact of these autoantibodies on C1 complex formation.

Main Methods:

• Plasma samples from 74 lupus nephritis patients were analyzed over 5 years using ELISA to detect anti-C1q, anti-C1r, anti-C1s, and anti-C1-Inh autoantibodies.
• IgG purification and surface plasmon resonance (SPR) were used to assess antibody binding and C1 complex formation.
• Correlations with clinical characteristics, disease activity (BILAG Renal score), and histological findings were examined.

Main Results:

• Anti-C1q autoantibodies were detected in 14.9% of patients, showing significant correlations with anti-dsDNA, anti-nuclear antibodies, C3, and C4 levels.
• High anti-C1q levels were associated with renal histologic lesions, histological activity index, and more severe disease classifications.
• Anti-C1r (4.2%), anti-C1s (6.9%), and anti-C1-Inh (0%) autoantibodies showed no significant correlation with clinical characteristics or impact on C1 complex formation.

Conclusions:

• Anti-C1q autoantibodies are significant contributors to the autoimmune pathology and severity of lupus nephritis.
• Autoantibodies against C1r and C1s do not appear to play a major pathogenic role or correlate with disease severity in this cohort.
• Further research into anti-C1q's role in LN pathogenesis is warranted.