Autoantibodies to complement components in C3 glomerulopathy and atypical hemolytic uremic syndrome

Area of Science:

• Immunology
• Nephrology
• Complement System

Background:

• The alternative pathway of complement plays a key role in the development of various kidney diseases, including atypical hemolytic uremic syndrome, dense deposit disease, and C3 glomerulopathy.
• These renal diseases are often caused by defects in the complement system, which can be either genetic or acquired, with autoantibodies representing a significant acquired factor.
• Distinguishing between genetic and autoimmune forms of these complement-mediated kidney diseases is critical, as autoimmune cases necessitate distinct therapeutic approaches.

Purpose of the Study:

• To provide a comprehensive overview of anti-complement autoantibodies implicated in renal diseases.
• To detail the characteristics of newly identified autoantibodies targeting the complement system.
• To highlight the similarities and differences among autoimmune forms of complement-mediated kidney diseases.

Main Methods:

• Literature review and synthesis of existing data on anti-complement autoantibodies.
• Summarization of autoantibodies targeting key complement components: factor H, factor I, C3b, and factor B.
• Description of autoantibodies against complement convertases, specifically C3 nephritic factor and C4 nephritic factor.

Main Results:

• Several types of anti-complement autoantibodies have been identified in patients with renal diseases.
• Autoantibodies against factor H, factor I, C3b, factor B, C3 nephritic factor, and C4 nephritic factor are discussed.
• Newly described autoantibodies and their specific characteristics are presented, offering insights into disease mechanisms.

Conclusions:

• Autoantibodies targeting the alternative complement pathway are significant contributors to the pathogenesis of C3 glomerulopathy and related renal disorders.
• The identification and characterization of these autoantibodies are essential for guiding treatment decisions, particularly in differentiating autoimmune from genetic causes.
• Understanding the spectrum and features of anti-complement autoantibodies is crucial for advancing the management of autoimmune renal diseases mediated by complement dysregulation.