Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune...

Area of Science:

• Immunogenetics
• Autoimmunity
• Complement System

Background:

• Copy number variation (CNV) in complement component 4 (C4A and C4B) is linked to systemic inflammatory autoimmune diseases.
• The relationship between C4 CNV and the autoimmune repertoire in specific diseases like systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), and myositis requires further investigation.

Purpose of the Study:

• To investigate the association between C4 copy number variation and the autoimmune repertoire in SLE, primary SS, and myositis.
• To determine if C4 CNV is connected to specific autoantibodies within these systemic inflammatory autoimmune diseases.

Main Methods:

• Targeted DNA sequencing was employed to determine C4 copy number and genetic variants.
• The study included 2,290 Scandinavian patients diagnosed with SLE, primary SS, or myositis, alongside 1,251 healthy controls.

Main Results:

• A significant association was found between C4A copy number and the presence of SSA/SSB autoantibodies across all three diseases.
• Individuals with zero C4A copies and both SSA/SSB autoantibodies exhibited a strong association (OR 18.0) compared to controls.
• Low C4A copy number correlated with reduced C4 plasma levels and impaired C4b deposition on immune complexes.

Conclusions:

• Low C4A copy number is more strongly associated with the autoantibody profile than with specific clinical disease entities.
• These findings suggest potential implications for understanding the etiopathogenesis of systemic inflammatory autoimmune diseases.
• Genetic profiling, specifically C4 CNV, may aid in patient stratification for these conditions.